Abstract
Vascular remodeling in host tissues surrounding growing tumors is implicated in the successful development of tumor neovasculature The vascular endothelial growth factor VEGF-A is a prime regulator of endothelial cell proliferation, angiogenesis, vasculogenesis, and vascular permeability. VEGF-C and -D induce both tumor angiogenesis and lymphangiogenesis, and promote the lymphatic spread of tumors. Angiopoietin-1 (Ang-1) plus VEGF-A cause an increased number of new blood vessels with evidence of a mature vascular system, while angiopoietin-2 (Ang-2) plus VEGF-A promote a rapid increase in capillary diameter, remodeling of the basal lamina, proliferation and migration of endothelial cells, and stimulated sprouting of new blood vessels in vivo. In this study, we have demonstrated that human angiosarcoma cells express VEGF-A, -C, and -D, VEGF receptors (Flt-1, KDR, and Flt-4), Ang-2, and Ang-1 and -2 receptor (Tie-2). These results suggest that the VEGF family and Ang-2 signaling pathway may play a role in the cell proliferation and growth of angio-sarcoma cells. We also found, that serum VEGF-D and Ang-2 protein levels increased as the tumor stage advanced in the angiosarcoma patients. VEGF-D and Ang-2 play important roles in tumor growth and metastatic tumor spread in angiosarcoma.
