**5.5.4 Repression of Tsp-1**

The anti-angiogenic molecule Tsp-1 is capable of inhibiting metalloproteinase-9 (MMP9) from releasing the VEGF sequestered in ECM. The oncoprotein Ras has been reported to increase VEGF expression and inhibit Tsp-1 expression. One study showed that the inhibitory function of Ras on Tsp-1 via PI3K pathway also involve RhoA and RhoC in human embryonic kidney cell lines, human mammary cell lines, and breast cancer cell lines (Watnick, Cheng et al. 2003). And the suppression of Tsp-1 always correlates with promotion of angiogenesis.
