Outside Influences

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Science  22 Jul 2005:
Vol. 309, Issue 5734, pp. 536
DOI: 10.1126/science.309.5734.536c

One of the current concepts in cancer research is that tumor epithelial cells do not grow in isolation, but in the context of a stromal microenvironment that can be permissive or nonpermissive for malignancy. Although this hypothesis was proposed many years ago, only recently have microenvironmental influences on tumorigenesis been explored at the level of specific cell types and signaling molecules.

Two papers focus on the cellular microenvironment in breast cancer. Radisky et al. describe a cascade of signaling events triggered in mouse mammary epithelial cells that are exposed to matrix metalloproteinase-3 (MMP-3), a stromal enzyme that is overexpressed in human breast cancer and that has been shown to confer tumorigenic potential to normal epithelial cells. These signaling events culminate in the production of reactive oxygen species (ROS) that damage DNA and cause genomic instability in the epithelial cells. Hu et al. investigated whether stromal cells in human breast cancer undergo genomic modifications that might influence stromal cell gene expression during tumorigenesis. An assay of genome-wide methylation revealed that epigenetic changes occur in stromal cells in a tumor stage- and cell type-specific manner, supporting the idea that the dialogue between tumor cells and microenvironment evolves as tumors progress. — PAK

Nature 436, 123 (2005); Nat. Genet. 10.1038/ng1596 (2005).

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