Oncostatin M-mediated regulation of matrix metalloproteinases and associated mediators of MMPs' expression in H-ras transformed fibroblasts

Oncostatin M (OSM) is a growth and differentiation factor which has been shown to exert both stimulatory and inhibitory effects on tissue invasion in various cell lines. Tissue invasion is a key marker of metastases and can be monitored by examining activities associated with ECM degradation such as matrix metalloproteinases (MMPs). This present study elucidates a link, between OSM, MMPs, and various mediators associated with MMP activity. Treatment of NR3 cells (H-ras transformed, benign tumor forming cells) with OSM resulted in a time and dose dependent induction of MMP-9 and MMP-2. MMP-9 and MMP-2 activity increased as early as 2 hours when exposed to OSM [200ng./ml]. Elevated MMP-9 and MMP-2 protein expression also occurred following treatment with OSM [50ng./ml] and this increase was maintained for 72 hours. The expression of other activities which affect MMP expression was determined in response to OSM treatment. EMMPRIN, RECK, TIMP-1, and TIMP-2 expression was determined. NR3 cells were exposed to OSM at 200ng./ml for 2 hours and 50ng./ml for 24 hours. Western blot analysis revealed that EMMPRIN protein expression increased dramatically, RECK protein expression decreased, TIMP-1 protein expression increased, and TIMP-2 showed no change at the protein expression level.These OSM-mediated alterations in MMPs and related activities represent an aspect of the altered phenotype which occurs following H-ras mediated cellular transformation of these cells.