Abstract

Endothelial cells are not just passive conduits for delivering blood to the tumor, but also endothelial cells are responsible for creating a tumor vascular niche and produce paracrine factors (angiocrine factors) that promote tumor growth. There is evidence to suggest that vasculature, mainly by angiogenesis, have a role in the progression of prostate cancer. Here, we investigated an alternative role for endothelial cells which is the biological influence of endothelium-derived angiocrine factors on prostate cancer epithelial cells. Using cell conditioned media (CM) collected from HUVEC (human umbilical vein endothelial cell) we studied the effect of paracrine stimulation on viability, proliferation, migration and invasion of prostate cancer cell lines (CaP) and the in-vivo effect was studied using co-injection of CaP cells with HUVEC or injection of CaP cells pre-incubated with CM using both, a zebrafish embryo and an immunodeficient-mouse model. Our results indicated that CM stimulated viability of CaP cell lines and selectively promote migration of more aggressive CaP cell line. We also observed that endothelial cells either through cell-cell interaction or by paracrine communication, enhanced tumor growth and increases tumor microvasculature in-vivo. These data suggest that paracrine factors released by the endothelium promote survival, migration and invasion in-vitro in more aggressive CaP cells and promote the tumor growth in vivo. These results provide evidences to suggest that the tumor-associated endothelium could contribute to the acquisition of a more advanced and metastatic phenotype of CaP.