Highway Deconstruction

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Science  06 Sep 2013:
Vol. 341, Issue 6150, pp. 1044
DOI: 10.1126/science.341.6150.1044-c

Because most cancer patients die of metastatic disease, there is substantial interest in understanding—and pharmacologically thwarting—the molecular events that drive or facilitate metastasis. Early in the process within the primary tumor, cells attach to and migrate along collagen networks, which take them to blood vessels that carry them to distant organs they ultimately colonize. A new study suggests that these collagen highways are particularly important for an aggressive soft-tissue sarcoma that frequently and fatally metastasizes to the lung. Using mouse models, Eisinger-Mathason et al. show that when primary sarcomas become deprived of oxygen, a transcription factor called HIF1α (hypoxia-inducible factor 1α) is induced, which in turn enhances the expression of PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), an enzyme that creates dense and highly disorganized networks of collagen by adding hydroxyl groups to collagen monomers. Sarcomas in mice treated with a drug known to inhibit PLOD2 expression (minoxidil, which is commonly used for hair restoration) exhibited more-organized patterns of collagen and had a reduced propensity to metastasize to the lung.

Cancer Discov. 3, 10.1158/2159-8290.CD-13-0118 (2013).

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