Novel Inhibitor of Tumor Angiogenenesis
Dr. Suneel S. Apte and colleagues at the Lerner Research Institute, Cleveland Clinic Foundation in Cleveland, OH have discovered that the metalloprotease ADAMTS9 inhibits tumor angiogenesis. They present these findings in the March 2010 issue of The American Journal of Pathology.
Angiogenesis, or the growth of new blood vessels, is a critical step in the transition of tumors from dormant to malignant. Therefore, angiogenesis inhibitors form a major therapeutic approach to cancer treatment.
The metalloprotease ADAMTS9 functions as a tumor suppressor in throat and nose cancer. Mice partially deficient for Adamts9 spontaneously form new blood vessels, suggesting that it may play an inhibitory role in tumor angiogenesis. Koo et al found that capillary cells in both healthy tissue and tumors expressed ADAMTS9. Moreover, mice that lack one copy of Adamts9 had a greater level of new vessel formation in tumors than wild-type mice, and blocking ADAMTS9 in vitro resulted in increased signs of vessel formation. Indeed, ADAMTS9 inhibits angiogenesis through a different mechanism than a similar molecule, ADAMTS1.
Dr. Apte and colleagues conclude that "ADAMTS9 may be of broad relevance to all angiogenesis-dependent cancers through its novel and constitutive expression in capillary [endothelial cells] and physiological anti-angiogenic role."
Koo B-H, Coe DM, Dixon LJ, Somerville RPT, Nelson CM, Wang LW, Young ME, Lindner DJ, Apte SS: ADAMTS9 is a cell-autonomously acting, anti-angiogenic metalloprotease expressed by microvascular endothelial cells. Am J Pathol 2010 176
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American Journal of Pathology