STKE: Facilitator for Carcinogenesis

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Science  03 Nov 2000:
Vol. 290, Issue 5493, pp. 903c
DOI: 10.1126/science.290.5493.903c

To grow and become invasive, tumor cells solicit aid from other cells, such as the vascular endothelial cells that form new blood vessels in the tissues that the cancer cells invade. Bergers et al. used a transgenic mouse model of multistage carcinogenesis to analyze the onset of angiogenesis during development of tumors of the pancreatic islets. They unexpectedly found that vascular endothelial growth factor (VEGF)—an established inducer of angiogenesis—and its receptors were constitutively expressed in islets and did not increase in abundance when angiogenesis began. Nevertheless, an inhibitor of VEGF signaling did inhibit angiogenesis and tumor growth. What did correlate with the onset of angiogenesis was expression of matrix metalloproteinase-9 (MMP-9), and expression of MMP-9 promoted angiogenesis and release of VEGF from cultured islets. In another mouse model of tumorigenesis, Coussens et al. find a similar facilitatory effect of MMP-9, and that it appears to be recruited from bone marrow-derived inflammatory cells. — LBR

Nature Cell Biol. 2, 737 (2000); Cell 103, 481 (2000).

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