Mu opioid receptor stimulates a growth promoting and pro-angiogenic tumor microenvironment

4650 We observed that morphine stimulates MAPK/ERK and PKB/Akt signaling in endothelial cells and promotes proliferation, migration and survival leading to increased angiogenesis and tumor growth in mice (Gupta et al 2002, Cancer Res). Morphine and other opioid analgesics are mu opioid receptor (MOR) agonists, which act centrally as well as peripherally directly and by modulating the secretion of cytokines. Therefore, we examined the role of MOR in endothelium and cancer progression using MOR deleted (MOR-KO) and wild type (wt) mice. We isolated and cultured blood outgrowth endothelial cells (BOEC) and implanted T241 fibrosarcoma tumor cells for in vitro and in vivo studies, respectively. MOR-KO derived BOEC assume round shape after 3 days in culture at P1 and undergo significant apoptosis Vs the wild type BOEC (p