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Oncostatin M‐ Mediated Regulation of Matrix Metalloproteinases and Associated Mediators of MMPs' Expression in H‐ras Transformed Fibroblasts
Author(s) -
Francis Edward Joseph,
Hurta Robert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a278-c
Subject(s) - oncostatin m , matrix metalloproteinase , western blot , cell culture , chemistry , microbiology and biotechnology , biology , cancer research , immunology , inflammation , interleukin 6 , biochemistry , gene , genetics
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. [N.S.E.R.C. & Canadian Cancer Society (P.E.I. Division)funded]