470 Endoglin Enhances the Progression of Angiosarcoma Through the Regulation of Non-Smad TGF-β Signaling

Angiosarcoma is a rare malignant tumor derived from endothelial cells and its prognosis is poor because advanced angiosarcoma is resistant to standard chemotherapy, and new therapies are urgently needed. Endoglin (CD105) is a membrane glycoprotein that acts as a coreceptor for transforming growth factor-β (TGF-β) signaling. Endoglin is overexpressed in the tumor-associated endothelial cells, and it enhances angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibody in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether the inhibition of endoglin may have anti-tumor activity. Endoglin protein levels in cultured angiosarcoma cells were increased compared to those in normal endothelial cells. Immunohistochemical analyses revealed that the expression of endoglin protein was strongly increased in angiosarcoma tissues compared with that in normal dermal vessels. Endoglin siRNA suppressed the proliferation, migration, invasion and Warburg effect of angiosarcoma cells. Knockdown of endoglin reduced the expression of survivin and the phosphorylation of Paxillin and VE cadherin. Besides, although endoglin is a co-receptor that regulates TGF-β signaling, anti-tumor effect of endoglin for angiosarcoma was not based on the regulation of Smad signaling, but non-Smad TGF-β signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma.