Here we demonstrate some novel points: (a) Expression of EMMPRIN is increased in tumor cells upon co-culturing with macrophages; (b) EMMPRIN is post-transcriptionally regulated by miRNA-146a; (c) Soluble EMMPRIN retains its biological activity, is required for maximal induction of both VEGF and MMP-9, and is generated by a serine protease that is yet to be identified; (d) soluble EMMPRIN alone has a pro-angiogenic activity and a direct effect on endothelial cells both in vitro and in vivo. The gene discussed is VEGFA; the disease is neoplasm.