TSP-1 Induced Apoptosis in Microvascular Endothelial Cell

As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.

Contributor: Glenn Croston, PhD

REFERENCES: Benilde Jimenez, Olga V. Volpert, Susan E. Crawford, Maria Febbraio, Roy L. Silberstein & Noel Bouck Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nature Medicine Jan 2000, Vol 6 #1 pp41-48