THE ROLE OF CB1 AND CB2 RECEPTORS IN CANNABIS INDUCED APOPTOSIS IN VITRO.

OPG binds to and inhibits TNF-Related Apoptosis Inducing Ligand (TRAIL), thereby potentially increasing the survival of tumour cells normally eliminated by this mechanism. We have investigated whether OPG produced by bone marrow stromal cells (BMSC) isolated from breast cancer patients has the potential to inhibit TRAIL-induced apoptosis of breast cancer cells in vitro, thereby increasing tumour cell survival rates. BMSC were isolated from breast cancer patients (following appropriate ethical approval), and OPG levels determined by ELISA. Breast cancer cells were exposed to TRAIL in the absence or presence of 50 % BMSC-conditioned medium, and the levels of apoptotic cell death evaluated. BMSC were found to produce substantial levels of OPG in vitro (45000pg/ml/96hours). In standard medium, TRAIL induced apoptotic cell death in the breast cancer cell line MDA-MB-436, (33%vs 0.6 % in control). When the breast cancer cells were exposed to TRAIL in BMSC-conditioned medium containing high levels of OPG, the levels of TRAIL-induced apoptosis were reduced by 50 % compared to standard medium. BMSC isolated from breast cancer patients produce sufficient levels of OPG in vitro to protect breast cancer cells from TRAIL-induced apoptosis. Our data suggest that bone-derived OPG may act as a survival factor for breast cancer cells in vitro. The in vivo significance of these findings remains to be clarified