MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response

摘要: Abstract The capacity of inducing angiogenesis is a recognized hallmark cancer cells. microenvironment, characterized by hypoxia and inflammatory signals, promotes proliferation, migration activation quiescent endothelial cells (EC) from surrounding vascular network. Current anti-angiogenic drugs present side effects, temporary efficacy, issues primary resistance, thereby calling for the identification new therapeutic targets. MICALs are unique family redox enzymes that destabilize F-actin in cytoskeletal dynamics. MICAL2 mediates Semaphorin3A-NRP2 response to VEGFR1 rat ECs. also enters p130Cas interactome VEGF HUVEC. Previously, we showed overexpressed metastatic cancer. A small-molecule inhibitor exists (CCG-1423). Here report 1) expressed neo-angiogenic ECs human solid tumors (kidney breast carcinoma, glioblastoma cardiac myxoma, n = 67, were analyzed with immunohistochemistry) animal models ischemia/inflammation neo-angiogenesis, but not normal capillary bed; 2) protein pharmacological inhibition (CCG-1423) or gene KD reduce EC viability functional performance; 3) disables vitro. Whole-genome expression profiling reveals involvement development pathways. Based on these results, propose participates inflammation-induced neo-angiogenesis should be tested cancer- noncancer-associated where chronic inflammation represents relevant pathophysiological mechanism.