Transformation of epithelial cells through recruitment leads to polyclonal intestinal tumors.

Thliveris AT, Schwefel B, Clipson L, Plesh L, Zahm CD, Leystra AA, Washington MK, Sullivan R, Deming DA, Newton MA, Halberg RB
Proc Natl Acad Sci U S A. 2013 110 (28): 11523-8

PMID: 23798428 · PMCID: PMC3710880 · DOI:10.1073/pnas.1303064110

Intestinal tumors from mice and humans can have a polyclonal origin. Statistical analyses indicate that the best explanation for this source of intratumoral heterogeneity is the presence of interactions among multiple progenitors. We sought to better understand the nature of these interactions. An initial progenitor could recruit others by facilitating the transformation of one or more neighboring cells. Alternatively, two progenitors that are independently initiated could simply cooperate to form a single tumor. These possibilities were tested by analyzing tumors from aggregation chimeras that were generated by fusing together embryos with unequal predispositions to tumor development. Strikingly, numerous polyclonal tumors were observed even when one genetic component was highly, if not completely, resistant to spontaneous tumorigenesis in the intestine. Moreover, the observed number of polyclonal tumors could be explained by the facilitated transformation of a single neighbor within 144 μm of an initial progenitor. These findings strongly support recruitment instead of cooperation. Thus, it is conceivable that these interactions are necessary for tumors to thrive, so blocking them might be a highly effective method for preventing the formation of tumors in the intestine and other tissues.

MeSH Terms (8)

Animals Cell Transformation, Neoplastic Epithelial Cells Genes, APC Humans Intestinal Neoplasms Mice Mice, Inbred C57BL

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