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

First Author  Thliveris AT Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  28 Pages  11523-8
PubMed ID  23798428 Mgi Jnum  J:198817
Mgi Id  MGI:5499259 Doi  10.1073/pnas.1303064110
Citation  Thliveris AT, et al. (2013) Transformation of epithelial cells through recruitment leads to polyclonal intestinal tumors. Proc Natl Acad Sci U S A 110(28):11523-8
abstractText  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 mum 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.
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