Angiogenesis-Independent Neovascularization is a Major Contributor to Tumor Growth
Final rept. 15 Feb 2004-15 Aug 2005
M D ANDERSON CANCER CENTER HOUSTON TX
Pagination or Media Count:
Tumors must manipulate the host vasculature to provide a blood supply adequate for their proliferation. Although tumors may arise as avascular masses. there is increasing evidence that some tumors begin to proliferate by coopting the host vasculature. By analyzing cell proliferation kinetics of endothelial cells EC and PC3 prostate cancer cells, we provide evidence that EC proliferation could not account for rapid tumor growth. Although PC3mm2 expressing green fluorescent protein GFP failed to grow in the ears, in an orthotopic GFP - expressing melanoma model we demonstrated that the tumor vasculature was generated from a preexisting red cell-deficient vascular network that continuously remodeled to accommodate the requirements of the expanding tumor mass. Topical application of vascular endothelial growth factor VEGF to vascular beds generated immediate and robust vascular transitions that were morphologically similar to tumor-induced vascular transitions. Nphi-nitro-L-arginine, a nitric oxide inhibitor that prevented VEGF-mediated vascular remodeling and vasodilatation, significantly inhibited prostate tumor growth without reducing EC proliferation. These findings suggest that prostate tumor-induced remodeling of red cell-deficient vessels, and not angiogenic sprouting, contributes to tumor vascularization and concomitant proliferation.
- Medicine and Medical Research