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Across the Entire Tree of Life – “Cell Cannibalism” Is Much More Common Than Scientists Thought

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Thursday, May 23, 2024

In addition to competing for resources, living cells actively kill and eat each other. New explorations of these “cell-in-cell” phenomena show they are not restricted to cancer cells but are a common facet of living organisms, across the tree of life. Credit: Jason Drees for the Biodesign Institute at Arizona State UniversityNew research reveals that cell-in-cell phenomena, where one cell consumes another, are common across all life forms and important for normal biological functions, not just associated with cancer.In a recent review paper, Carlo Maley and his team at Arizona State University explore the cell-in-cell phenomena where one cell engulfs and sometimes consumes another. The study shows that cases of this behavior, including cell cannibalism, are widespread across the tree of life.The findings challenge the common perception that cell-in-cell events are largely restricted to cancer cells. Rather, these events appear to be common across diverse organisms, from single-celled amoeba to complex multicellular animals.The widespread occurrence of such interactions in non-cancer cells suggests that these events are not inherently “selfish” or “cancerous” behaviors. Rather, the researchers propose that cell-in-cell phenomena may play crucial roles in normal development, homeostasis, and stress response across a wide range of organisms. The study argues that targeting cell-in-cell events as an approach to treating cancer should be abandoned, as these phenomena are not unique to malignancy.By demonstrating that occurrences span a wide array of life forms and are deeply rooted in our genetic makeup, the research invites us to reconsider fundamental concepts of cellular cooperation, competition, and the intricate nature of multicellularity. The study opens new avenues for research in evolutionary biology, oncology, and regenerative medicine.The new research, published in the Nature journal Scientific Reports, is the first to systematically investigate cell-in-cell phenomena across the tree of life. The group’s findings could help redefine the understanding of cellular behavior and its implications for multicellularity, cancer, and the evolutionary journey of life itself.Carlo Maley is a researcher with the Biodesign Center for Biocomputing, Security and Society; professor in the School of Life Sciences at ASU; and director of the Arizona Cancer Evolution Center. Credit: The Biodesign Institute at Arizona State University“We first got into this work because we learned that cells don’t just compete for resources — they actively kill and eat each other,” Maley says. “That’s a fascinating aspect of the ecology of cancer cells. But further exploration revealed that these phenomena happen in normal cells, and sometimes neither cell dies, resulting in an entirely new type of hybrid cell.”Maley is a researcher with the Biodesign Center for Biocomputing, Security and Society; professor in the School of Life Sciences at ASU; and director of the Arizona Cancer Evolution Center.The study was conducted in collaboration with first author Stefania E. Kapsetaki, formerly with ASU and now a researcher at Tufts University, and Luis Cisneros, formerly with ASU and currently a researcher at Mayo Clinic.From selfish to cooperative cell interactionsCell-in-cell events have long been observed but remain poorly understood, especially outside the context of immune responses or cancer. The earliest genes responsible for cell-in-cell behavior date back over 2 billion years, suggesting the phenomena play an important, though yet-to-be-determined, role in living organisms. Understanding the diverse functions of cell-in-cell events, both in normal physiology and disease, is important for developing more effective cancer therapies.The review delves into the occurrence, genetic underpinnings, and evolutionary history of cell-in-cell phenomena, shedding light on a behavior once thought to be an anomaly. The researchers reviewed more than 500 articles to catalog the various forms of cell-in-cell phenomena observed across the tree of life.The study describes 16 different taxonomic groups in which cell-in-cell behavior is found to occur. The cell-in-cell events were classified into six distinct categories based on the degree of relatedness between the host and prey cells, as well as the outcome of the interaction (whether one or both cells survived).A spectrum of cell-in-cell behaviors are highlighted in the study, ranging from completely selfish acts, where one cell kills and consumes another, to more cooperative interactions, where both cells remain alive. For example, the researchers found evidence of “heterospecific killing,” where a cell engulfs and kills a cell of a different species, across a wide range of unicellular, facultatively multicellular, and obligate multicellular organisms. In contrast, “conspecific killing,” where a cell consumes another cell of the same species, was less common, observed in only three of the seven major taxonomic groups examined.Obligate multicellular organisms are those that must exist in a multicellular form throughout their life cycle. They cannot survive or function as single cells. Examples include most animals and plants. Facultative multicellular organisms are organisms that can exist either as single cells or in a multicellular form depending on environmental conditions. For example, certain types of algae may live as single cells in some conditions but form multicellular colonies in others.The team also documented cases of cell-in-cell phenomena where both the host and prey cells remained alive after the interaction, suggesting these events may serve important biological functions beyond just killing competitors.“Our categorization of cell-in-cell phenomena across the tree of life is important for better understanding the evolution and mechanism of these phenomena,” Kapsetaki says. “Why and how exactly do they happen? This is a question that requires further investigation across millions of living organisms, including organisms where cell-in-cell phenomena may not yet have been searched for.”Ancient genesIn addition to cataloging the diverse cell-in-cell behaviors, the researchers also investigated the evolutionary origins of the genes involved in these processes. Surprisingly, they found that many of the key cell-in-cell genes emerged long before the evolution of obligate multicellularity.“When we look at genes associated with known cell-in-cell mechanisms in species that diverged from the human lineage a very long time ago, it turns out that the human orthologs (genes that evolved from a common ancestral gene) are typically associated with normal functions of multicellularity, like immune surveillance,” Cisneros says.In total, 38 genes associated with cell-in-cell phenomena were identified, and 14 of these originated over 2.2 billion years ago, predating the common ancestor of some facultatively multicellular organisms. This suggests that the molecular machinery for cell cannibalism evolved before the major transitions to complex multicellularity.The ancient cell-in-cell genes identified in the study are involved in a variety of cellular processes, including cell–cell adhesion, phagocytosis (engulfment), intracellular killing of pathogens, and regulation of energy metabolism. This diversity of functions indicates that cell-in-cell events likely served important roles even in single-celled and simple multicellular organisms well before the emergence of complex multicellular life.Reference: “Cell-in-cell phenomena across the tree of life” by Stefania E. Kapsetaki, Luis H. Cisneros and Carlo C. Maley, 29 March 2024, Scientific Reports.DOI: 10.1038/s41598-024-57528-7

New research reveals that cell-in-cell phenomena, where one cell consumes another, are common across all life forms and important for normal biological functions, not just...

Cell in Cell Phenomena

In addition to competing for resources, living cells actively kill and eat each other. New explorations of these “cell-in-cell” phenomena show they are not restricted to cancer cells but are a common facet of living organisms, across the tree of life. Credit: Jason Drees for the Biodesign Institute at Arizona State University

New research reveals that cell-in-cell phenomena, where one cell consumes another, are common across all life forms and important for normal biological functions, not just associated with cancer.

In a recent review paper, Carlo Maley and his team at Arizona State University explore the cell-in-cell phenomena where one cell engulfs and sometimes consumes another. The study shows that cases of this behavior, including cell cannibalism, are widespread across the tree of life.

The findings challenge the common perception that cell-in-cell events are largely restricted to cancer cells. Rather, these events appear to be common across diverse organisms, from single-celled amoeba to complex multicellular animals.

The widespread occurrence of such interactions in non-cancer cells suggests that these events are not inherently “selfish” or “cancerous” behaviors. Rather, the researchers propose that cell-in-cell phenomena may play crucial roles in normal development, homeostasis, and stress response across a wide range of organisms.

The study argues that targeting cell-in-cell events as an approach to treating cancer should be abandoned, as these phenomena are not unique to malignancy.

By demonstrating that occurrences span a wide array of life forms and are deeply rooted in our genetic makeup, the research invites us to reconsider fundamental concepts of cellular cooperation, competition, and the intricate nature of multicellularity. The study opens new avenues for research in evolutionary biology, oncology, and regenerative medicine.

The new research, published in the Nature journal Scientific Reports, is the first to systematically investigate cell-in-cell phenomena across the tree of life. The group’s findings could help redefine the understanding of cellular behavior and its implications for multicellularity, cancer, and the evolutionary journey of life itself.

Carlo Maley

Carlo Maley is a researcher with the Biodesign Center for Biocomputing, Security and Society; professor in the School of Life Sciences at ASU; and director of the Arizona Cancer Evolution Center. Credit: The Biodesign Institute at Arizona State University

“We first got into this work because we learned that cells don’t just compete for resources — they actively kill and eat each other,” Maley says. “That’s a fascinating aspect of the ecology of cancer cells. But further exploration revealed that these phenomena happen in normal cells, and sometimes neither cell dies, resulting in an entirely new type of hybrid cell.”

Maley is a researcher with the Biodesign Center for Biocomputing, Security and Society; professor in the School of Life Sciences at ASU; and director of the Arizona Cancer Evolution Center.

The study was conducted in collaboration with first author Stefania E. Kapsetaki, formerly with ASU and now a researcher at Tufts University, and Luis Cisneros, formerly with ASU and currently a researcher at Mayo Clinic.

From selfish to cooperative cell interactions

Cell-in-cell events have long been observed but remain poorly understood, especially outside the context of immune responses or cancer. The earliest genes responsible for cell-in-cell behavior date back over 2 billion years, suggesting the phenomena play an important, though yet-to-be-determined, role in living organisms. Understanding the diverse functions of cell-in-cell events, both in normal physiology and disease, is important for developing more effective cancer therapies.

The review delves into the occurrence, genetic underpinnings, and evolutionary history of cell-in-cell phenomena, shedding light on a behavior once thought to be an anomaly. The researchers reviewed more than 500 articles to catalog the various forms of cell-in-cell phenomena observed across the tree of life.

The study describes 16 different taxonomic groups in which cell-in-cell behavior is found to occur. The cell-in-cell events were classified into six distinct categories based on the degree of relatedness between the host and prey cells, as well as the outcome of the interaction (whether one or both cells survived).

A spectrum of cell-in-cell behaviors are highlighted in the study, ranging from completely selfish acts, where one cell kills and consumes another, to more cooperative interactions, where both cells remain alive. For example, the researchers found evidence of “heterospecific killing,” where a cell engulfs and kills a cell of a different species, across a wide range of unicellular, facultatively multicellular, and obligate multicellular organisms. In contrast, “conspecific killing,” where a cell consumes another cell of the same species, was less common, observed in only three of the seven major taxonomic groups examined.

Obligate multicellular organisms are those that must exist in a multicellular form throughout their life cycle. They cannot survive or function as single cells. Examples include most animals and plants. Facultative multicellular organisms are organisms that can exist either as single cells or in a multicellular form depending on environmental conditions. For example, certain types of algae may live as single cells in some conditions but form multicellular colonies in others.

The team also documented cases of cell-in-cell phenomena where both the host and prey cells remained alive after the interaction, suggesting these events may serve important biological functions beyond just killing competitors.

“Our categorization of cell-in-cell phenomena across the tree of life is important for better understanding the evolution and mechanism of these phenomena,” Kapsetaki says. “Why and how exactly do they happen? This is a question that requires further investigation across millions of living organisms, including organisms where cell-in-cell phenomena may not yet have been searched for.”

Ancient genes

In addition to cataloging the diverse cell-in-cell behaviors, the researchers also investigated the evolutionary origins of the genes involved in these processes. Surprisingly, they found that many of the key cell-in-cell genes emerged long before the evolution of obligate multicellularity.

“When we look at genes associated with known cell-in-cell mechanisms in species that diverged from the human lineage a very long time ago, it turns out that the human orthologs (genes that evolved from a common ancestral gene) are typically associated with normal functions of multicellularity, like immune surveillance,” Cisneros says.

In total, 38 genes associated with cell-in-cell phenomena were identified, and 14 of these originated over 2.2 billion years ago, predating the common ancestor of some facultatively multicellular organisms. This suggests that the molecular machinery for cell cannibalism evolved before the major transitions to complex multicellularity.

The ancient cell-in-cell genes identified in the study are involved in a variety of cellular processes, including cell–cell adhesion, phagocytosis (engulfment), intracellular killing of pathogens, and regulation of energy metabolism. This diversity of functions indicates that cell-in-cell events likely served important roles even in single-celled and simple multicellular organisms well before the emergence of complex multicellular life.

Reference: “Cell-in-cell phenomena across the tree of life” by Stefania E. Kapsetaki, Luis H. Cisneros and Carlo C. Maley, 29 March 2024, Scientific Reports.
DOI: 10.1038/s41598-024-57528-7

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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.

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Dead, sick pelicans turning up along Oregon coast

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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.

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

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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. 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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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Animals
Conservation
Documentary

Wild Florida's Vanishing Call

A moving, powerful inside look at what has happened to the wild, rarely seen, real Florida. A compelling, emotional soundtrack carries the viewer through the past destruction of wild Florida habitats, to beautiful scenes of Florida's rarely seen native wild animals, including the most endangered cat in North America, the Florida Panther, and ends with a positive message encouraging the viewer to work to protect Florida's wildlife and habitat before it is too late.

Animals
Nature
Music

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