TitleEvolution of cooperation among tumor cells
Uniform TitleProceedings of the National Academy of Sciences of the United States of America
PublisherNational Academy of Sciences
NameAxelrod, Robert (author), Axelrod, David E. (author), Pienta, Kenneth J. (author), National Institutes of Health (U.S.), National Science Foundation (U.S.), New Jersey Commission on Cancer Research,
DescriptionThe evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the issue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell???stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as byproduct mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.
NoteAuthor manuscript. Published in final edited form as: Proc Natl Acad Sci U S A. 2006 September 5; 103(36): 13474-13479.
NoteThe final published version of this article is located at: www.pnas.org/cgi/doi/10.1073/pnas.0606053103
NoteNIH U56 CA113004; to David E. Axelrod
NoteR.A. was supported by National Science Foundation (NSF) Grant SES-0240852. D.E.A. was supported by NSF Grant IIS-0312953, National Institutes of Health (NIH) Grant U56 CA113004, and New Jersey Commission on Cancer Research Grant 1076-CCR-SO. K.J.P. is an American Cancer Society Clinical Research Professor and is supported by NIH Grants CA69568, CA102872, and CA093900.
NoteNIH CA69568; to Kenneth J. Pienta
NoteNIH CA102872; to Kenneth J. Pienta
NoteNIH CA093900; to Kenneth J. Pienta
NoteNSF SES-0240852; to Robert Axelrod
NoteNJ Commission on Cancer Research 1076-CCR-SO; to David E. Axelrod
NoteAlso available in PubMed Central. PMCID: PMC1557388
CollectionAxelrod, David Collection
Organization NameRutgers, The State University of New Jersey
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