Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Abstract

Recent reports have described several cellular phenotypes that appear to be mediated by endosialin/TEM-1/CD248 (TeM-1), including tubule formation on matrigel, migration and proliferation. It has been shown that siRNa knock-down of TeM-1 in primary human fibroblasts resulted in reduced proliferation. however, the downstream signaling events that mediate TeM-1 function(s) currently remain unknown. In this study, we demonstrate that TeM-1 mediates proliferation of primary human pericytes through a pDGF receptor signaling pathway. Normal pericytes expressing high levels of TeM-1 were able to proliferate, respond to pDGF-BB stimulation by phosphorylating both the pDGF receptor and the Map kinase eRK-1/2, and induce the expression of the immediate early transcription factor c-Fos. however, when TeM-1 expression was knocked-down, pDGF-BB-induced proliferation, eRK-1/2 phosphorylation, and c-Fos expression were significantly impaired. Thus, our results provide evidence for a TeM-1-dependent signal pathway that controls proliferation of human pericytes and suggest targeting this pathway for future strategies aimed at mitigating tumor angiogenesis. © 2010 Landes Bioscience.