Non-cell autonomous tumor-growth driving supports sub-clonal heterogeneity
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CitationMarusyk, Andriy, Doris P. Tabassum, Philipp M. Altrock, Vanessa Almendro, Franziska Michor, and Kornelia Polyak. 2014. “Non-cell autonomous tumor-growth driving supports sub-clonal heterogeneity.” Nature 514 (7520): 54-58. doi:10.1038/nature13556. http://dx.doi.org/10.1038/nature13556.
AbstractSUMMARY Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumors. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumor phenotypes and the competitive expansion of individual clones. We found that tumor growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumor by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumor collapse. We then developed a mathematical modeling framework to identify the rules underlying the generation of intratumor clonal heterogeneity. We found that non-cell autonomous driving, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.
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