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How Do Cancer Cells Migrate to New Tissues and Take Hold?

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Friday, April 4, 2025

How Do Cancer Cells Migrate to New Tissues and Take Hold? Scientists are looking for answers about how these confounding trips, known as metastases, occur throughout the human body Illustration of a human cancer cell SCIEPRO / SCIENCE PHOTO LIBRARY via Getty Images Back in 2014, a woman with advanced cancer pushed Adrienne Boire’s scientific life in a whole new direction. The cancer, which had begun in the breast, had found its way into the patient’s spinal fluid, rendering the middle-aged mother of two unable to walk. “When did this happen?” she asked from her hospital bed. “Why are the cells growing there?” Why, indeed. Why would cancer cells migrate to the spinal fluid, far from where they’d been birthed, and how did they manage to thrive in a liquid so strikingly poor in nutrients? Boire, a physician-scientist at Memorial Sloan Kettering Cancer Center in New York, decided that those questions deserved answers. The answers are urgent, because the same thing that happened to Boire’s patient is happening to increasing numbers of cancer patients. As the ability to treat initial, or primary, tumors has improved, people survive early rounds with cancer only to come back years or decades later when the cancer has somehow resettled in a new tissue, such as brain, lung or bone. This is metastatic cancer, and it’s the big killer—while precise numbers are scarce, anywhere from half to the large majority of cancer deaths have been attributed to metastasis. Offering people more options and hope will mean understanding how those cancers successfully migrate and recolonize. The prevalence of metastasis belies the arduous journey that cancer cells must make to achieve it. A cell that arises in, say, the breast, is well adapted to live there: to eat the fatty acids available to it, to resist local threats and to grow there in a solid tumor. If it manages to escape into the bloodstream, it finds itself zipping along at up to 15 inches per second with shear stresses sufficient to rip it apart. Should it survive that odyssey and land in a new tissue—say, the brain or spinal fluid—the environment is totally different yet again. The foods the cell is accustomed to may be absent; immune cells or other novel environmental molecules may attack. For a cell to manage this trip, and then adapt to a new environment, is truly a Herculean task. “It is not easy and trivial,” says Ana Gomes, a cancer biologist at the Moffitt Cancer Center in Tampa, Florida. “It’s just against everything in the nature of these cells.” Moving to a new site and forming a new tumor is an arduous journey that few cells can complete. A cell must exit the initial tumor, survive the bloodstream and enter a new tissue. Even then, the cell may remain dormant for a time, until the environment can support its division and growth to create a new tumor. Adapted from Ana Gomes / Knowable Magazine No wonder that, even though tumors regularly shed cells, most escapees perish or languish without successfully establishing themselves as metastases. “Personally, I think metastasis is an accident,” says Matthew Vander Heiden, a physician-scientist and director of the Koch Institute for Integrative Cancer Research at MIT. “It’s really, really inefficient.” The few cells that manage this epic feat are resilient and flexible in how they feed themselves and process the molecules around them. They may tweak their biochemistry to evade local dangers, or to get the fuel they need in sparse environments. Some even send signals ahead to modify the organ where they’ll land, creating a cushy nest with a food supply ready for when they arrive. “Metabolic changes help these cells to face all this challenge,” says Patricia Altea-Manzano, a biomedical researcher at the Andalusian Molecular Biology and Regenerative Medicine Center in Seville, Spain. Such findings suggest ways that metastasizing cells, because they’re so different from the original tumor, might be vulnerable to new kinds of treatment. Someday doctors might not have to wait for metastasis to take hold before they block or slow cancer’s spread: “That is a very big opportunity,” Gomes says. Novel adaptations Metabolically, there’s no place like home: Cancers tend to do best in the tissues where they initially grow, Vander Heiden’s group has found. And when they do move, these primary tumors have preferred target sites—prostate cancers tend to move into bone, for example. Some cells, however, will land in a place to which they are very unlikely to ever adapt: Certain sites, such as the spleen and skeletal muscles, seem to resist metastasis, and there are many possible reasons. Muscle cells, for example, use tons of energy, causing their mitochondria to release lots of a side product of energy processing: reactive oxygen species such as hydrogen peroxide. These vigorously oxidizing molecules are toxic, but local muscle cells can handle them. Yet even though plenty of tumor cells reach the skeletal muscle via the blood that copiously feeds it, they rarely take hold there, stymied, researchers suspect, by those reactive oxygen molecules. But adaptation to other novel environments is possible, as Vander Heiden discovered when his group implanted human breast cancer cells into either mammary fat or the brains of mice. Though the brain lacks the kinds of fat building blocks—fatty acids—that breast cancer cells are accustomed to eating, when the cells were dropped into the brain, they adjusted to manufacture their own fatty acids. The scientists then treated the mice with a drug that blocks fatty acid synthesis, and the cancer cells in brain tissue grew at half-speed. (The breast cells in the mammary fat continued to grow unbothered.) Vander Heiden has consulted for companies that are in the early stages of exploring this approach as a treatment. Sometimes, tumors can even prime a foreign site for their arrival, in a process some researchers call “education of the metastatic niche.” Cancers shed not only cells, but also hormones, DNA and little fatty bubbles called vesicles into the blood and lymph. These bubbles can contain chemical messages, and when these or other signals reach far-off organs, they can reshape the tissues to the tumor cells’ specifications. That “education” helps set up metastasizing cells to thrive in a new location says Gomes. Even microbes can get in on the act: In the case of colorectal cancer, bacteria from the intestines teach the liver to receive metastatic cancer cells. The gut bacteria colonize the intestinal tumor, then break through the multilayer barrier that normally keeps gut contents away from the rest of the body. Then the bacteria can go into the liver, where they induce inflammation in the organ. This creates a pro-tumor environment, so cancer cells that arrive later are able to settle in. The fatty acid connection Altea-Manzano studied this priming process during her time as a postdoctoral scholar with cancer biologist Sarah-Maria Fendt at the VIB-KU Leuven Center for Cancer Biology in Belgium. In this case, it was the lungs that were being primed by tumors residing elsewhere. And much as Vander Heiden observed with breast cancer metastasis to the brain, access to fatty acids was a key factor—specifically, the fatty acid palmitate, whose functions include serving as an energy source and as a component of cellular membranes. The lungs are already awash in a fat-rich material called surfactant, which coats the lungs’ interior and keeps the tissue from collapsing. When the researchers fed mice a high-fat diet, the levels of palmitate and other fatty acids in the lungs rose. And when the researchers injected mouse mammary (breast) cancer cells into the blood of those mice, the high-fat diet resulted in more than twice as much metastasis to the lung. To check whether tumor cells were secreting something that primed the lungs to host them, Altea-Manzano and colleagues grew pieces of mouse mammary tumor in a dish, then collected the liquid containing all the cellular secretions. When they injected this cell-free soup into mice, it boosted the palmitate levels in the lungs; if they also injected cancer cells, this treatment increased the level of lung metastases by those cells, too. Some ingredient made by the cancer cells cultured in that lab dish was sending the lungs a message: Make more palmitate. (The scientists still aren’t sure what the signaling substance is.) The result is that if a breast cancer cell lands in the lungs, it finds a fatty, ready-made feast to nosh on. To make the most of the new menu, however, a newly arrived breast cancer cell will have to alter its cell chemistry. It does that by changing its mitochondria so they can take up more palmitate. In experiments with mice, blocking that change interfered with metastasis, no matter how much palmitate was present. It might do the same in human patients, speculates Altea-Manzano, who with Fendt and others was a co-author of a discussion of metabolic changes that might promote or thwart metastasis for the 2024 Annual Review of Cancer Biology. A person’s lifestyle as well as their environment can influence their metabolism and microbiome. That, in turn, can be a factor in the success or failure of cancer to metastasize. But the relationships are complex: Things that seem good for metabolism on the surface—such as antioxidants—aren’t always things that directly counter cancer spread. Adapted from A. Vandekeere et al. / AR Cancer Biology 2024 / Knowable Magazine Knowing the enemy In addition to fat-rich places like the lungs, cancers can adapt to surprisingly challenging locales, such as the barren wasteland that is the spinal fluid surrounding the brain and spinal cord. Most places in the body where tumors originate are replete with nutrients: fats, amino acids, oxygen, metals—all the foodstuffs a rapidly growing cell needs. In contrast, “the brain is kind of a metabolic princess,” says Boire. “It prefers glucose only, please.” Not only is there precious little to eat, but cancer cells will find themselves surrounded by support cells of the nervous system and resident immune cells, both of which spew out anti-tumor agents. Boire’s work focuses on the spinal fluid. It’s a clear liquid devoid of many nutrients, and yet metastasis to the spinal fluid happens in some 5 percent to 10 percent of solid-tumor patients, and it usually kills within months. For Boire, this makes such a cancer “a worthy adversary. … It’s totally evil.” To learn how such an evil cell survives, Boire and colleagues examined metastatic cells from five patients in whom breast or lung cancers had taken over the spinal fluid. These cells had all ramped up a biochemical system that sops up iron, a necessary metal to produce energy and more cell parts. As one part of the system, the cells secreted a protein called lipocalin-2 that collects the sparse iron in the environment; for the other part, they made a protein called a lipocalin-2-iron transporter that pulls the iron-lipocalin-2 complex into the cells. Mice studied as models for metastasis to the spinal fluid normally all die within fewer than 40 days. But when scientists treated the mice with a drug, deferoxamine, that prevents the cancer from accessing iron, they live for longer. Adapted from Y. Chi et al. / Science 2020 / Knowable Magazine Studying the process further in mice, Boire’s team discovered that the cancer cells boost their iron collection in response to inflammatory molecules produced by local immune cells. The cancer cells then slurp up so much iron that the immune cells can’t meet their own needs for the metal. “They’re like the original jerks at the buffet,” says Boire. “You know these guys—they’re taking everything you want for themselves.” To starve out these cellular creeps, the researchers treated mice with a molecule called deferoxamine that snatches the iron before lipocalin-2 has a chance to grab it. Sure enough, the iron levels in the cancer cells dropped. Moreover, the mice survived nearly twice as long as animals who didn’t get the treatment. Boire has begun testing deferoxamine in a few dozen patients who have metastatic cancer in the spinal fluid and expects to publish results soon. She notes that the treatment doesn’t act directly on the cancer but changes its environment so it can’t fulfill its needs. “It kind of opens up this idea—there are other ways of targeting cancer cell growth,” she says. Stress points In addition to food, traveling cancer cells need protection from changes to their metabolism in new environments. Metastasis itself seems to cause cancer cells to generate reactive oxygen species, which can kill them from within, says Sean Morrison, a cancer biologist at the University of Texas Southwestern Medical Center in Dallas. His team studies this metastasis roadblock by injecting human melanoma cells into mice. The scientists can put the cells right under the skin where they should be comfortable, or stick them into other places, such as the bloodstream or spleen, to see if they can achieve metastasis. In the skin, melanoma cells don’t experience much oxidative stress. But melanoma cells in the blood or other organs experience stress from higher levels of reactive oxygen molecule levels. It could be that higher levels of iron and oxygen in places like the blood drive biochemical changes that produce these dangerous molecules, Morrison suggests. Oxidative stress kills wandering melanoma cells by a process called ferroptosis, in which polyunsaturated fatty acids in the cancer cell membrane react with iron. “It’s like a grease fire starting in the cancer cells as they’re trying to migrate,” says Morrison. But some melanoma cells gain a defense if they cruise the body’s lymphatic system before settling down. In the lymph, their membranes pick up monounsaturated fatty acids that can’t react with iron in the same way, helping them resist ferroptosis, the researchers reported. That’s not all. Melanoma cells that were the most efficient at metastasis rewired their metabolism, the scientists found. As a result, they gorged on a molecule called lactate in their surroundings, and they seemed to use this lactate to manufacture protective, oxidant-fighting molecules. When the scientists blocked the ability of the melanoma cells to suck up this lactate, metastatic disease in the mice was reduced. In contrast, when they treated mice with more antioxidants, metastasizing cells were more likely to survive in the bloodstream and other organs—in some treated mice, the numbers of metastatic cells cruising the bloodstream more than doubled. That result, published in 2015, was a huge surprise, says Morrison: “People think of antioxidants as being good for you.” Well, in his lab mice, antioxidants were good for cancer cells too—really good. The Washington Post called the study “terrifying,” “provocative” and “alarming.” In an experiment, scientists studied a line of mice that had melanoma injected under their skin. Treatment with an antioxidant greatly increased the fraction of cells in blood that were metastasizing melanoma cells (left), as well as the burden—quantity—of metastatic cancer cells in their internal organs (right). Adapted from E. Piskounova et al. / Nature 2015 / Knowable Magazine But the results do jive with past trials of antioxidants in cancer patients. In studies spanning decades, antioxidants such as beta-carotene and vitamin E were linked to increased lung cancer rates and deaths in smokers and higher prostate cancer rates in healthy men. Although those studies did not focus on metastatic cancer, Morrison sees a connection. “The reality is that at certain key phases of the evolution of cancer, the cancer cells are just on the edge of dying of oxidative stress, so they benefit more from the antioxidants than the normal cells do,” he speculates. If antioxidants are good for cancers, then boosting reactive oxygen molecules might fight some kinds of metastasis. Indeed, some current cancer treatments do amplify reactive oxygen molecules to kill cancers. These results imply that diet choices or supplements might influence cancer and metastasis risk. For example, Morrison speculates that a diet high in polyunsaturated fatty acids might lead to more of those pro-ferroptosis fatty acids in the membranes of cancer cells. If the cells are already quite vulnerable, a bit of polyunsaturated fat might be another way to nudge them over the cliff to cell death. For once, that’s an easy diet to swallow: One menu item might be salmon seared in soybean oil, Morrison suggests. Dietary change is not going to vanquish cancer on its own, Fendt says. But, she adds, it might slow progression or help other treatments to work—although as the antioxidant trials illustrate, the effects of diet can be tricky to predict. “It’s important to have really solid and rigorous science on those questions,” cautions Fendt. Some trials are underway—but, for now, there’s no “anti-metastasis” diet to prescribe.Knowable Magazine is an independent journalistic endeavor from Annual Reviews. Get the latest Science stories in your inbox.

Scientists are looking for answers about how these confounding trips, known as metastases, occur throughout the human body

How Do Cancer Cells Migrate to New Tissues and Take Hold?

Scientists are looking for answers about how these confounding trips, known as metastases, occur throughout the human body

Cancer Cell Illustration
Illustration of a human cancer cell SCIEPRO / SCIENCE PHOTO LIBRARY via Getty Images

Back in 2014, a woman with advanced cancer pushed Adrienne Boire’s scientific life in a whole new direction. The cancer, which had begun in the breast, had found its way into the patient’s spinal fluid, rendering the middle-aged mother of two unable to walk. “When did this happen?” she asked from her hospital bed. “Why are the cells growing there?”

Why, indeed. Why would cancer cells migrate to the spinal fluid, far from where they’d been birthed, and how did they manage to thrive in a liquid so strikingly poor in nutrients?

Boire, a physician-scientist at Memorial Sloan Kettering Cancer Center in New York, decided that those questions deserved answers.

The answers are urgent, because the same thing that happened to Boire’s patient is happening to increasing numbers of cancer patients. As the ability to treat initial, or primary, tumors has improved, people survive early rounds with cancer only to come back years or decades later when the cancer has somehow resettled in a new tissue, such as brain, lung or bone. This is metastatic cancer, and it’s the big killer—while precise numbers are scarce, anywhere from half to the large majority of cancer deaths have been attributed to metastasis. Offering people more options and hope will mean understanding how those cancers successfully migrate and recolonize.

The prevalence of metastasis belies the arduous journey that cancer cells must make to achieve it. A cell that arises in, say, the breast, is well adapted to live there: to eat the fatty acids available to it, to resist local threats and to grow there in a solid tumor. If it manages to escape into the bloodstream, it finds itself zipping along at up to 15 inches per second with shear stresses sufficient to rip it apart. Should it survive that odyssey and land in a new tissue—say, the brain or spinal fluid—the environment is totally different yet again. The foods the cell is accustomed to may be absent; immune cells or other novel environmental molecules may attack. For a cell to manage this trip, and then adapt to a new environment, is truly a Herculean task.

“It is not easy and trivial,” says Ana Gomes, a cancer biologist at the Moffitt Cancer Center in Tampa, Florida. “It’s just against everything in the nature of these cells.”

Metastasis Graphic
Moving to a new site and forming a new tumor is an arduous journey that few cells can complete. A cell must exit the initial tumor, survive the bloodstream and enter a new tissue. Even then, the cell may remain dormant for a time, until the environment can support its division and growth to create a new tumor. Adapted from Ana Gomes / Knowable Magazine

No wonder that, even though tumors regularly shed cells, most escapees perish or languish without successfully establishing themselves as metastases. “Personally, I think metastasis is an accident,” says Matthew Vander Heiden, a physician-scientist and director of the Koch Institute for Integrative Cancer Research at MIT. “It’s really, really inefficient.”

The few cells that manage this epic feat are resilient and flexible in how they feed themselves and process the molecules around them. They may tweak their biochemistry to evade local dangers, or to get the fuel they need in sparse environments. Some even send signals ahead to modify the organ where they’ll land, creating a cushy nest with a food supply ready for when they arrive. “Metabolic changes help these cells to face all this challenge,” says Patricia Altea-Manzano, a biomedical researcher at the Andalusian Molecular Biology and Regenerative Medicine Center in Seville, Spain.

Such findings suggest ways that metastasizing cells, because they’re so different from the original tumor, might be vulnerable to new kinds of treatment. Someday doctors might not have to wait for metastasis to take hold before they block or slow cancer’s spread: “That is a very big opportunity,” Gomes says.

Novel adaptations

Metabolically, there’s no place like home: Cancers tend to do best in the tissues where they initially grow, Vander Heiden’s group has found. And when they do move, these primary tumors have preferred target sites—prostate cancers tend to move into bone, for example.

Some cells, however, will land in a place to which they are very unlikely to ever adapt: Certain sites, such as the spleen and skeletal muscles, seem to resist metastasis, and there are many possible reasons. Muscle cells, for example, use tons of energy, causing their mitochondria to release lots of a side product of energy processing: reactive oxygen species such as hydrogen peroxide. These vigorously oxidizing molecules are toxic, but local muscle cells can handle them. Yet even though plenty of tumor cells reach the skeletal muscle via the blood that copiously feeds it, they rarely take hold there, stymied, researchers suspect, by those reactive oxygen molecules.

But adaptation to other novel environments is possible, as Vander Heiden discovered when his group implanted human breast cancer cells into either mammary fat or the brains of mice. Though the brain lacks the kinds of fat building blocks—fatty acids—that breast cancer cells are accustomed to eating, when the cells were dropped into the brain, they adjusted to manufacture their own fatty acids.

The scientists then treated the mice with a drug that blocks fatty acid synthesis, and the cancer cells in brain tissue grew at half-speed. (The breast cells in the mammary fat continued to grow unbothered.) Vander Heiden has consulted for companies that are in the early stages of exploring this approach as a treatment.

Sometimes, tumors can even prime a foreign site for their arrival, in a process some researchers call “education of the metastatic niche.” Cancers shed not only cells, but also hormones, DNA and little fatty bubbles called vesicles into the blood and lymph. These bubbles can contain chemical messages, and when these or other signals reach far-off organs, they can reshape the tissues to the tumor cells’ specifications. That “education” helps set up metastasizing cells to thrive in a new location says Gomes.

Even microbes can get in on the act: In the case of colorectal cancer, bacteria from the intestines teach the liver to receive metastatic cancer cells. The gut bacteria colonize the intestinal tumor, then break through the multilayer barrier that normally keeps gut contents away from the rest of the body. Then the bacteria can go into the liver, where they induce inflammation in the organ. This creates a pro-tumor environment, so cancer cells that arrive later are able to settle in.

The fatty acid connection

Altea-Manzano studied this priming process during her time as a postdoctoral scholar with cancer biologist Sarah-Maria Fendt at the VIB-KU Leuven Center for Cancer Biology in Belgium. In this case, it was the lungs that were being primed by tumors residing elsewhere. And much as Vander Heiden observed with breast cancer metastasis to the brain, access to fatty acids was a key factor—specifically, the fatty acid palmitate, whose functions include serving as an energy source and as a component of cellular membranes.

The lungs are already awash in a fat-rich material called surfactant, which coats the lungs’ interior and keeps the tissue from collapsing. When the researchers fed mice a high-fat diet, the levels of palmitate and other fatty acids in the lungs rose. And when the researchers injected mouse mammary (breast) cancer cells into the blood of those mice, the high-fat diet resulted in more than twice as much metastasis to the lung.

To check whether tumor cells were secreting something that primed the lungs to host them, Altea-Manzano and colleagues grew pieces of mouse mammary tumor in a dish, then collected the liquid containing all the cellular secretions. When they injected this cell-free soup into mice, it boosted the palmitate levels in the lungs; if they also injected cancer cells, this treatment increased the level of lung metastases by those cells, too. Some ingredient made by the cancer cells cultured in that lab dish was sending the lungs a message: Make more palmitate. (The scientists still aren’t sure what the signaling substance is.)

The result is that if a breast cancer cell lands in the lungs, it finds a fatty, ready-made feast to nosh on. To make the most of the new menu, however, a newly arrived breast cancer cell will have to alter its cell chemistry. It does that by changing its mitochondria so they can take up more palmitate. In experiments with mice, blocking that change interfered with metastasis, no matter how much palmitate was present. It might do the same in human patients, speculates Altea-Manzano, who with Fendt and others was a co-author of a discussion of metabolic changes that might promote or thwart metastasis for the 2024 Annual Review of Cancer Biology.

Metastasis Risk Graphic
A person’s lifestyle as well as their environment can influence their metabolism and microbiome. That, in turn, can be a factor in the success or failure of cancer to metastasize. But the relationships are complex: Things that seem good for metabolism on the surface—such as antioxidants—aren’t always things that directly counter cancer spread. Adapted from A. Vandekeere et al. / AR Cancer Biology 2024 / Knowable Magazine

Knowing the enemy

In addition to fat-rich places like the lungs, cancers can adapt to surprisingly challenging locales, such as the barren wasteland that is the spinal fluid surrounding the brain and spinal cord.

Most places in the body where tumors originate are replete with nutrients: fats, amino acids, oxygen, metals—all the foodstuffs a rapidly growing cell needs. In contrast, “the brain is kind of a metabolic princess,” says Boire. “It prefers glucose only, please.”

Not only is there precious little to eat, but cancer cells will find themselves surrounded by support cells of the nervous system and resident immune cells, both of which spew out anti-tumor agents.

Boire’s work focuses on the spinal fluid. It’s a clear liquid devoid of many nutrients, and yet metastasis to the spinal fluid happens in some 5 percent to 10 percent of solid-tumor patients, and it usually kills within months. For Boire, this makes such a cancer “a worthy adversary. … It’s totally evil.”

To learn how such an evil cell survives, Boire and colleagues examined metastatic cells from five patients in whom breast or lung cancers had taken over the spinal fluid. These cells had all ramped up a biochemical system that sops up iron, a necessary metal to produce energy and more cell parts. As one part of the system, the cells secreted a protein called lipocalin-2 that collects the sparse iron in the environment; for the other part, they made a protein called a lipocalin-2-iron transporter that pulls the iron-lipocalin-2 complex into the cells.

Mice and Iron Survival Graphic
Mice studied as models for metastasis to the spinal fluid normally all die within fewer than 40 days. But when scientists treated the mice with a drug, deferoxamine, that prevents the cancer from accessing iron, they live for longer. Adapted from Y. Chi et al. / Science 2020 / Knowable Magazine

Studying the process further in mice, Boire’s team discovered that the cancer cells boost their iron collection in response to inflammatory molecules produced by local immune cells. The cancer cells then slurp up so much iron that the immune cells can’t meet their own needs for the metal. “They’re like the original jerks at the buffet,” says Boire. “You know these guys—they’re taking everything you want for themselves.”

To starve out these cellular creeps, the researchers treated mice with a molecule called deferoxamine that snatches the iron before lipocalin-2 has a chance to grab it. Sure enough, the iron levels in the cancer cells dropped. Moreover, the mice survived nearly twice as long as animals who didn’t get the treatment.

Boire has begun testing deferoxamine in a few dozen patients who have metastatic cancer in the spinal fluid and expects to publish results soon.

She notes that the treatment doesn’t act directly on the cancer but changes its environment so it can’t fulfill its needs. “It kind of opens up this idea—there are other ways of targeting cancer cell growth,” she says.

Stress points

In addition to food, traveling cancer cells need protection from changes to their metabolism in new environments. Metastasis itself seems to cause cancer cells to generate reactive oxygen species, which can kill them from within, says Sean Morrison, a cancer biologist at the University of Texas Southwestern Medical Center in Dallas.

His team studies this metastasis roadblock by injecting human melanoma cells into mice. The scientists can put the cells right under the skin where they should be comfortable, or stick them into other places, such as the bloodstream or spleen, to see if they can achieve metastasis.

In the skin, melanoma cells don’t experience much oxidative stress. But melanoma cells in the blood or other organs experience stress from higher levels of reactive oxygen molecule levels. It could be that higher levels of iron and oxygen in places like the blood drive biochemical changes that produce these dangerous molecules, Morrison suggests.

Oxidative stress kills wandering melanoma cells by a process called ferroptosis, in which polyunsaturated fatty acids in the cancer cell membrane react with iron. “It’s like a grease fire starting in the cancer cells as they’re trying to migrate,” says Morrison.

But some melanoma cells gain a defense if they cruise the body’s lymphatic system before settling down. In the lymph, their membranes pick up monounsaturated fatty acids that can’t react with iron in the same way, helping them resist ferroptosis, the researchers reported.

That’s not all. Melanoma cells that were the most efficient at metastasis rewired their metabolism, the scientists found. As a result, they gorged on a molecule called lactate in their surroundings, and they seemed to use this lactate to manufacture protective, oxidant-fighting molecules. When the scientists blocked the ability of the melanoma cells to suck up this lactate, metastatic disease in the mice was reduced.

In contrast, when they treated mice with more antioxidants, metastasizing cells were more likely to survive in the bloodstream and other organs—in some treated mice, the numbers of metastatic cells cruising the bloodstream more than doubled.

That result, published in 2015, was a huge surprise, says Morrison: “People think of antioxidants as being good for you.” Well, in his lab mice, antioxidants were good for cancer cells too—really good. The Washington Post called the study “terrifying,” “provocative” and “alarming.”

Antioxidants and Metastasis Graphic
In an experiment, scientists studied a line of mice that had melanoma injected under their skin. Treatment with an antioxidant greatly increased the fraction of cells in blood that were metastasizing melanoma cells (left), as well as the burden—quantity—of metastatic cancer cells in their internal organs (right). Adapted from E. Piskounova et al. / Nature 2015 / Knowable Magazine

But the results do jive with past trials of antioxidants in cancer patients. In studies spanning decades, antioxidants such as beta-carotene and vitamin E were linked to increased lung cancer rates and deaths in smokers and higher prostate cancer rates in healthy men. Although those studies did not focus on metastatic cancer, Morrison sees a connection. “The reality is that at certain key phases of the evolution of cancer, the cancer cells are just on the edge of dying of oxidative stress, so they benefit more from the antioxidants than the normal cells do,” he speculates.

If antioxidants are good for cancers, then boosting reactive oxygen molecules might fight some kinds of metastasis. Indeed, some current cancer treatments do amplify reactive oxygen molecules to kill cancers.

These results imply that diet choices or supplements might influence cancer and metastasis risk. For example, Morrison speculates that a diet high in polyunsaturated fatty acids might lead to more of those pro-ferroptosis fatty acids in the membranes of cancer cells. If the cells are already quite vulnerable, a bit of polyunsaturated fat might be another way to nudge them over the cliff to cell death. For once, that’s an easy diet to swallow: One menu item might be salmon seared in soybean oil, Morrison suggests.

Dietary change is not going to vanquish cancer on its own, Fendt says. But, she adds, it might slow progression or help other treatments to work—although as the antioxidant trials illustrate, the effects of diet can be tricky to predict.

“It’s important to have really solid and rigorous science on those questions,” cautions Fendt. Some trials are underway—but, for now, there’s no “anti-metastasis” diet to prescribe.

Knowable

Knowable Magazine is an independent journalistic endeavor from Annual Reviews.

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Lifesize herd of puppet animals begins climate action journey from Africa to Arctic Circle

The Herds project from the team behind Little Amal will travel 20,000km taking its message on environmental crisis across the worldHundreds of life-size animal puppets have begun a 20,000km (12,400 mile) journey from central Africa to the Arctic Circle as part of an ambitious project created by the team behind Little Amal, the giant puppet of a Syrian girl that travelled across the world.The public art initiative called The Herds, which has already visited Kinshasa and Lagos, will travel to 20 cities over four months to raise awareness of the climate crisis. Continue reading...

Hundreds of life-size animal puppets have begun a 20,000km (12,400 mile) journey from central Africa to the Arctic Circle as part of an ambitious project created by the team behind Little Amal, the giant puppet of a Syrian girl that travelled across the world.The public art initiative called The Herds, which has already visited Kinshasa and Lagos, will travel to 20 cities over four months to raise awareness of the climate crisis.It is the second major project from The Walk Productions, which introduced Little Amal, a 12-foot puppet, to the world in Gaziantep, near the Turkey-Syria border, in 2021. The award-winning project, co-founded by the Palestinian playwright and director Amir Nizar Zuabi, reached 2 million people in 17 countries as she travelled from Turkey to the UK.The Herds’ journey began in Kinshasa’s Botanical Gardens on 10 April, kicking off four days of events. It moved on to Lagos, Nigeria, the following week, where up to 5,000 people attended events performed by more than 60 puppeteers.On Friday the streets of Dakar in Senegal will be filled with more than 40 puppet zebras, wildebeest, monkeys, giraffes and baboons as they run through Médina, one of the busiest neighbourhoods, where they will encounter a creation by Fabrice Monteiro, a Belgium-born artist who lives in Senegal, and is known for his large-scale sculptures. On Saturday the puppets will be part of an event in the fishing village of Ngor.The Herds’ 20,000km journey began in Kinshasa, the Democratic Republic of the Congo. Photograph: Berclaire/walk productionsThe first set of animal puppets was created by Ukwanda Puppetry and Designs Art Collective in Cape Town using recycled materials, but in each location local volunteers are taught how to make their own animals using prototypes provided by Ukwanda. The project has already attracted huge interest from people keen to get involved. In Dakar more than 300 artists applied for 80 roles as artists and puppet guides. About 2,000 people will be trained to make the puppets over the duration of the project.“The idea is that we’re migrating with an ever-evolving, growing group of animals,” Zuabi told the Guardian last year.Zuabi has spoken of The Herds as a continuation of Little Amal’s journey, which was inspired by refugees, who often cite climate disaster as a trigger for forced migration. The Herds will put the environmental emergency centre stage, and will encourage communities to launch their own events to discuss the significance of the project and get involved in climate activism.The puppets are created with recycled materials and local volunteers are taught how to make them in each location. Photograph: Ant Strack“The idea is to put in front of people that there is an emergency – not with scientific facts, but with emotions,” said The Herds’ Senegal producer, Sarah Desbois.She expects thousands of people to view the four events being staged over the weekend. “We don’t have a tradition of puppetry in Senegal. As soon as the project started, when people were shown pictures of the puppets, they were going crazy.”Little Amal, the puppet of a Syrian girl that has become a symbol of human rights, in Santiago, Chile on 3 January. Photograph: Anadolu/Getty ImagesGrowing as it moves, The Herds will make its way from Dakar to Morocco, then into Europe, including London and Paris, arriving in the Arctic Circle in early August.

Dead, sick pelicans turning up along Oregon coast

So far, no signs of bird flu but wildlife officials continue to test the birds.

Sick and dead pelicans are turning up on Oregon’s coast and state wildlife officials say they don’t yet know why. The Oregon Department of Fish and Wildlife says it has collected several dead brown pelican carcasses for testing. Lab results from two pelicans found in Newport have come back negative for highly pathogenic avian influenza, also known as bird flu, the agency said. Avian influenza was detected in Oregon last fall and earlier this year in both domestic animals and wildlife – but not brown pelicans. Additional test results are pending to determine if another disease or domoic acid toxicity caused by harmful algal blooms may be involved, officials said. In recent months, domoic acid toxicity has sickened or killed dozens of brown pelicans and numerous other wildlife in California. The sport harvest for razor clams is currently closed in Oregon – from Cascade Head to the California border – due to high levels of domoic acid detected last fall.Brown pelicans – easily recognized by their large size, massive bill and brownish plumage – breed in Southern California and migrate north along the Oregon coast in spring. Younger birds sometimes rest on the journey and may just be tired, not sick, officials said. If you find a sick, resting or dead pelican, leave it alone and keep dogs leashed and away from wildlife. State wildlife biologists along the coast are aware of the situation and the public doesn’t need to report sick, resting or dead pelicans. — Gosia Wozniacka covers environmental justice, climate change, the clean energy transition and other environmental issues. Reach her at gwozniacka@oregonian.com or 971-421-3154.Our journalism needs your support. Subscribe today to OregonLive.com.

50-Million-Year-Old Footprints Open a 'Rare Window' Into the Behaviors of Extinct Animals That Once Roamed in Oregon

Scientists revisited tracks made by a shorebird, a lizard, a cat-like predator and some sort of large herbivore at what is now John Day Fossil Beds National Monument

50-Million-Year-Old Footprints Open a ‘Rare Window’ Into the Behaviors of Extinct Animals That Once Roamed in Oregon Scientists revisited tracks made by a shorebird, a lizard, a cat-like predator and some sort of large herbivore at what is now John Day Fossil Beds National Monument Sarah Kuta - Daily Correspondent April 24, 2025 4:59 p.m. Researchers took a closer look at fossilized footprints—including these cat-like tracks—found at John Day Fossil Beds National Monument in Oregon. National Park Service Between 29 million and 50 million years ago, Oregon was teeming with life. Shorebirds searched for food in shallow water, lizards dashed along lake beds and saber-toothed predators prowled the landscape. Now, scientists are learning more about these prehistoric creatures by studying their fossilized footprints. They describe some of these tracks, discovered at John Day Fossil Beds National Monument, in a paper published earlier this year in the journal Palaeontologia Electronica. John Day Fossil Beds National Monument is a nearly 14,000-acre, federally protected area in central and eastern Oregon. It’s a well-known site for “body fossils,” like teeth and bones. But, more recently, paleontologists have been focusing their attention on “trace fossils”—indirect evidence of animals, like worm burrows, footprints, beak marks and impressions of claws. Both are useful for understanding the extinct creatures that once roamed the environment, though they provide different kinds of information about the past. “Body fossils tell us a lot about the structure of an organism, but a trace fossil … tells us a lot about behaviors,” says lead author Conner Bennett, an Earth and environmental scientist at Utah Tech University, to Crystal Ligori, host of Oregon Public Broadcasting’s “All Things Considered.” Oregon's prehistoric shorebirds probed for food the same way modern shorebirds do, according to the researchers. Bennett et al., Palaeontologia Electronica, 2025 For the study, scientists revisited fossilized footprints discovered at the national monument decades ago. Some specimens had sat in museum storage since the 1980s. They analyzed the tracks using a technique known as photogrammetry, which involved taking thousands of photographs to produce 3D models. These models allowed researchers to piece together some long-gone scenes. Small footprints and beak marks were discovered near invertebrate trails, suggesting that ancient shorebirds were pecking around in search of a meal between 39 million and 50 million years ago. This prehistoric behavior is “strikingly similar” to that of today’s shorebirds, according to a statement from the National Park Service. “It’s fascinating,” says Bennett in the statement. “That is an incredibly long time for a species to exhibit the same foraging patterns as its ancestors.” Photogrammetry techniques allowed the researchers to make 3D models of the tracks. Bennett et al., Palaeontologia Electronica, 2025 Researchers also analyzed a footprint with splayed toes and claws. This rare fossil was likely made by a running lizard around 50 million years ago, according to the team. It’s one of the few known reptile tracks in North America from that period. An illustration of a nimravid, an extinct, cat-like predator NPS / Mural by Roger Witter They also found evidence of a cat-like predator dating to roughly 29 million years ago. A set of paw prints, discovered in a layer of volcanic ash, likely belonged to a bobcat-sized, saber-toothed predator resembling a cat—possibly a nimravid of the genus Hoplophoneus. Since researchers didn’t find any claw marks on the paw prints, they suspect the creature had retractable claws, just like modern cats do. A set of three-toed, rounded hoofprints indicate some sort of large herbivore was roaming around 29 million years ago, probably an ancient tapir or rhinoceros ancestor. Together, the fossil tracks open “a rare window into ancient ecosystems,” says study co-author Nicholas Famoso, paleontology program manager at the national monument, in the statement. “They add behavioral context to the body fossils we’ve collected over the years and help us better understand the climate and environmental conditions of prehistoric Oregon,” he adds. Get the latest stories in your inbox every weekday.

Two teens and 5,000 ants: how a smuggling bust shed new light on a booming trade

Two Belgian 19-year-olds have pleaded guilty to wildlife piracy – part of a growing trend of trafficking ‘less conspicuous’ creatures for sale as exotic petsPoaching busts are familiar territory for the officers of Kenya Wildlife Service (KWS), an armed force tasked with protecting the country’s iconic creatures. But what awaited guards when they descended in early April on a guesthouse in the west of the country was both larger and smaller in scale than the smuggling operations they typically encounter. There were more than 5,000 smuggled animals, caged in their own enclosures. Each one, however, was about the size of a little fingernail: 18-25mm.The cargo, which two Belgian teenagers had apparently intended to ship to exotic pet markets in Europe and Asia, was ants. Their enclosures were a mixture of test tubes and syringes containing cotton wool – environments that authorities say would keep the insects alive for weeks. Continue reading...

Poaching busts are familiar territory for the officers of Kenya Wildlife Service (KWS), an armed force tasked with protecting the country’s iconic creatures. But what awaited guards when they descended in early April on a guesthouse in the west of the country was both larger and smaller in scale than the smuggling operations they typically encounter. There were more than 5,000 smuggled animals, caged in their own enclosures. Each one, however, was about the size of a little fingernail: 18-25mm.The samples of garden ants presented to the court. Photograph: Monicah Mwangi/ReutersThe cargo, which two Belgian teenagers had apparently intended to ship to exotic pet markets in Europe and Asia, was ants. Their enclosures were a mixture of test tubes and syringes containing cotton wool – environments that authorities say would keep the insects alive for weeks.“We did not come here to break any laws. By accident and stupidity we did,” says Lornoy David, one of the Belgian smugglers.David and Seppe Lodewijckx, both 19 years old, pleaded guilty after being charged last week with wildlife piracy, alongside two other men in a separate case who were caught smuggling 400 ants. The cases have shed new light on booming global ant trade – and what authorities say is a growing trend of trafficking “less conspicuous” creatures.These crimes represent “a shift in trafficking trends – from iconic large mammals to lesser-known yet ecologically critical species”, says a KWS statement.The unusual case has also trained a spotlight on the niche world of ant-keeping and collecting – a hobby that has boomed over the past decade. The seized species include Messor cephalotes, a large red harvester ant native to east Africa. Queens of the species grow to about 20-24mm long, and the ant sales website Ants R Us describes them as “many people’s dream species”, selling them for £99 per colony. The ants are prized by collectors for their unique behaviours and complex colony-building skills, “traits that make them popular in exotic pet circles, where they are kept in specialised habitats known as formicariums”, KWS says.Lornoy David and Seppe Lodewijckx during the hearing. Photograph: Monicah Mwangi/ReutersOne online ant vendor, who asked not to be named, says the market is thriving, and there has been a growth in ant-keeping shows, where enthusiasts meet to compare housing and species details. “Sales volumes have grown almost every year. There are more ant vendors than before, and prices have become more competitive,” he says. “In today’s world, where most people live fast-paced, tech-driven lives, many are disconnected from themselves and their environment. Watching ants in a formicarium can be surprisingly therapeutic,” he says.David and Lodewijckx will remain in custody until the court considers a pre-sentencing report on 23 April. The ant seller says theirs is a “landmark case in the field”. “People travelling to other countries specifically to collect ants and then returning with them is virtually unheard of,” he says.A formicarium at a pet shop in Singapore. Photograph: Roslan Rahman/AFP/Getty ImagesScientists have raised concerns that the burgeoning trade in exotic ants could pose a significant biodiversity risk. “Ants are traded as pets across the globe, but if introduced outside of their native ranges they could become invasive with dire environmental and economic consequences,” researchers conclude in a 2023 paper tracking the ant trade across China. “The most sought-after ants have higher invasive potential,” they write.Removing ants from their ecosystems could also be damaging. Illegal exportation “not only undermines Kenya’s sovereign rights over its biodiversity but also deprives local communities and research institutions of potential ecological and economic benefits”, says KWS. Dino Martins, an entomologist and evolutionary biologist in Kenya, says harvester ants are among the most important insects on the African savannah, and any trade in them is bound to have negative consequences for the ecology of the grasslands.A Kenyan official arranges the containers of ants at the court. Photograph: Kenya Wildlife Service/AP“Harvester ants are seed collectors, and they gather [the seeds] as food for themselves, storing these in their nests. A single large harvester ant colony can collect several kilos of seeds of various grasses a year. In the process of collecting grass seeds, the ants ‘drop’ a number … dispersing them through the grasslands,” says Martins.The insects also serve as food for various other species including aardvarks, pangolins and aardwolves.Martins says he is surprised to see that smugglers feeding the global “pet” trade are training their sights on Kenya, since “ants are among the most common and widespread of insects”.“Insect trade can actually be done more sustainably, through controlled rearing of the insects. This can support livelihoods in rural communities such as the Kipepeo Project which rears butterflies in Kenya,” he says. Locally, the main threats to ants come not from the illegal trade but poisoning from pesticides, habitat destruction and invasive species, says Martins.Philip Muruthi, a vice-president for conservation at the African Wildlife Foundation in Nairobi, says ants enrich soils, enabling germination and providing food for other species.“When you see a healthy forest … you don’t think about what is making it healthy. It is the relationships all the way from the bacteria to the ants to the bigger things,” he says.

Belgian Teenagers Found With 5,000 Ants to Be Sentenced in 2 Weeks

Two Belgian teenagers who were found with thousands of ants valued at $9,200 and allegedly destined for European and Asian markets will be sentenced in two weeks

NAIROBI, Kenya (AP) — Two Belgian teenagers who were found with thousands of ants valued at $9,200 and allegedly destined for European and Asian markets will be sentenced in two weeks, a Kenyan magistrate said Wednesday.Magistrate Njeri Thuku, sitting at the court in Kenya’s main airport, said she would not rush the case but would take time to review environmental impact and psychological reports filed in court before passing sentence on May 7.Belgian nationals Lornoy David and Seppe Lodewijckx, both 19 years old, were arrested on April 5 with 5,000 ants at a guest house. They were charged on April 15 with violating wildlife conservation laws.The teens have told the magistrate that they didn’t know that keeping the ants was illegal and were just having fun.The Kenya Wildlife Service had said the case represented “a shift in trafficking trends — from iconic large mammals to lesser-known yet ecologically critical species.”Kenya has in the past fought against the trafficking of body parts of larger wild animals such as elephants, rhinos and pangolins among others.The Belgian teens had entered the country on a tourist visa and were staying in a guest house in the western town of Naivasha, popular among tourists for its animal parks and lakes.Their lawyer, Halima Nyakinyua Magairo, told The Associated Press on Wednesday that her clients did not know what they were doing was illegal. She said she hoped the Belgian embassy in Kenya could “support them more in this judicial process.”In a separate but related case, Kenyan Dennis Ng’ang’a and Vietnamese Duh Hung Nguyen were charged after they were found in possession of 400 ants in their apartment in the capital, Nairobi.KWS had said all four suspects were involved in trafficking the ants to markets in Europe and Asia, and that the species included messor cephalotes, a distinctive, large and red-colored harvester ant native to East Africa.The ants are bought by people who keep them as pets and observe them in their colonies. Several websites in Europe have listed different species of ants for sale at varied prices.The 5,400 ants found with the four men are valued at 1.2 million Kenyan shillings ($9,200), according to KWS.Copyright 2025 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.Photos You Should See - Feb. 2025

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