In a review paper published by Carlo Maley and colleagues from Arizona State University, the concept of cell-in-cell phenomena, where one cell engulfs and sometimes consumes another, is explored. Contrary to common belief that such events are restricted to cancer cells, the study reveals that these interactions are widespread across diverse organisms, from single-celled amoebas to complex multicellular animals. The researchers propose that these phenomena may play crucial roles in normal development, homeostasis, and stress response in various organisms, challenging the notion that they are inherently selfish or cancerous behavior.
The research suggests that targeting cell-in-cell events as an approach to treating cancer should be reconsidered, as these phenomena are not unique to malignancy. By demonstrating the occurrence of such interactions in a wide array of life forms and their deep rootedness in genetic makeup, the study prompts a reevaluation of fundamental concepts of cellular cooperation, competition, and the nature of multicellularity. These findings could open new avenues for research in fields like evolutionary biology, oncology, and regenerative medicine, reshaping the understanding of cellular behavior and its implications for cancer and the evolutionary journey of life.
The study is the first to systematically investigate cell-in-cell phenomena across the tree of life, and the researchers’ findings could potentially redefine the understanding of cellular behavior and its impact on multicellularity, cancer, and evolutionary processes. Maley and his team began exploring these phenomena to understand the ecology of cancer cells, only to discover that such interactions also occur in normal cells, leading to the formation of novel hybrid cells. Collaborating researchers from Tufts University and Mayo Clinic contributed to the comprehensive analysis of cell-in-cell events, shedding light on the diversity and significance of these behaviors.
Cell-in-cell events have long been observed but remain poorly understood outside the context of immune responses or cancer. The study investigates the genetic underpinnings and evolutionary history of these phenomena, highlighting the diverse functions they may play in organisms. By reviewing over 500 articles, the researchers identify 16 different taxonomic groups where cell-in-cell behavior occurs, classified into six distinct categories based on relatedness between host and prey cells and the outcome of the interaction. The spectrum of behaviors ranges from completely selfish acts to cooperative interactions, providing insight into the complex nature of these events across a variety of organisms.
The research delves into the evolutionary origins of genes associated with cell-in-cell phenomena, revealing that many key genes emerged long before obligate multicellularity. Surprisingly, the study found that genes associated with these processes have ancient origins, predating the evolution of complex multicellularity. Genes involved in cell adhesion, phagocytosis, intracellular killing, and energy regulation are identified as playing roles in cell-in-cell events that likely served important functions in single-celled and simple multicellular organisms. The findings highlight the importance of understanding the mechanism and evolution of these phenomena across millions of organisms to gain insights into their biological significance.
The research team also documented cases where both host and prey cells survived interactions, suggesting these events may have essential biological functions beyond competition and killing competitors. This categorization of cell-in-cell phenomena across the tree of life provides a framework for further investigations into the evolutionary and mechanistic aspects of these behaviors, calling for expanded research across diverse organisms to unravel the complexities of cell interactions in living systems. As we delve deeper into the world of cell-in-cell phenomena, new perspectives on cellular cooperation, competition, and the intricacies of multicellularity emerge, challenging conventional thinking and offering novel insights into fundamental biological processes.