Endostatin Action through Integrins

Science's STKE  06 Feb 2001:
Vol. 2001, Issue 68, pp. tw1
DOI: 10.1126/stke.2001.68.tw1

Endostatin is a cleavage product of an extracellular matrix (ECM) collagen and is a potent inhibitor of angiogenesis. Yet, its mechanism of action has not been clear. Rehn et al. propose that endostatin may act as a ligand for certain endothelial integrins, cellular adhesion molecules that have long been implicated in regulating angiogenesis and tumorigenesis. Endostatin interacted with α5-and αv-integrins on the surface of endothelial cells. When presented as an immobilized substrate, endostatins promoted cell adhesion, motility, and survival in an integrin-dependent manner and also induced signaling events downstream of activated integrins. In contrast, soluble endostatin acted as an integrin antagonist and inhibited these functions. Hence, modulating integrins may be one means by which endostatins act. The finding further increases the repertoire of molecules associated with the ECM that inhibit angiogenesis.

M. Rehn, T. Veikkola, E. Kukk-Valdre, H. Nakamura, M. Ilmonen, C.R. Lombardo, T. Pihlajaniemi, K. Alitalo, K. Vuori, Interaction of endostatin with integrins implicated in angiogenesis. Proc. Natl. Acad. Sci. U.S.A. 98: 1024-1029 (2001). [Abstract] [Full Text]