Unstable Neighbors

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Science  12 Jan 2007:
Vol. 315, Issue 5809, pp. 163
DOI: 10.1126/science.315.5809.163c

Solid tumors may be conceptualized as a malignant mass of epithelial cells, but in fact they contain normal cells such as fibroblasts and the endothelial and smooth muscle cells that compose tumor blood vessels. The molecular conversations between malignant cells and these stromal cells can profoundly influence tumor growth; thus, stromal cells have become possible targets for cancer therapy. In contrast to tumor cells, stromal cells are widely believed to be genetically stable and hence would not be expected to develop resistance to therapy.

Pelham et al. have investigated the possibility that tumor-associated stromal cells, like their malignant neighbors, acquire genetic alterations during tumor progression. They used high-resolution DNA copy-number analysis to study human breast and colorectal tumors that had grown in mice for 30 to 150 days, an experimental design that allowed the stromal components to be readily identified by virtue of their mouse origin. Surprisingly, the stromal cells had undergone amplification or deletion of several genes, some of which can plausibly be linked to tumorigenesis. The magnitude of the genetic changes suggests that clones of mutant host cells had been selected for during tumor establishment or progression. Whether these changes reflect a selective pressure placed on stromal cells by the tumor in order to invoke a favorable microenvironment or, conversely, a host-initiated selection of mutant stromal cells designed to suppress tumor progression is not yet clear. — PAK

Proc. Natl. Acad. Sci. U.S.A. 103, 19848 (2006).

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