On the Contradictory Effects of Oncostatin M in Human Breast Cancer

Publication Date


Type of Culminating Activity


Degree Title

Masters of Science in Biology



Major Advisor

Cheryl L. Jorcyk


Julia T. Oxford


Denise G. Wingett


Oncostatin M (OSM) is a pleiotropic cytokine in the IL-6 family and is produced by many different cell types, including human T-lymphocytes, macrophanges and monocytes. The data on the effects of OSM on tumor cell lines have shown contradictory results. Many laboratories have shown that OSM decreases tumor cell proliferation, indicating it may slow or stop tumor growth. However, in vitro data from our laboratory suggests that OSM may promote breast tumor progression and metastasis by enhancing angiogenesis, cell detachment, and invasiveness. The enhancement of angiogenesis occurs through the induction of vascular endothelial growth factor (VEGF), and may occur through the stabilization of the transcription factor HIF1α. In vitro studies have shown that HIf1α inhibitor, NSC134754, blocks OSM-induction of VEGF and in vivo Matrigel plug angiogenesis assay data indicate that the inhibitor blocks most, but not all, angiogenic signals from MDA-MB-213 human breast cancer cell conditioned media

In vivo studies have proven difficult due to the lack of identity between human OSM and other species. In an attempt to understand OSM’s functions in vivo we attempted to create cell lines that stably overexpress human OSM. However, due to the growth inhibitory properties of OSM we were unable to reach this goal. We, instead, have used a mouse xenograft model to analyze human breast cancer. Mice were injected subcutaneously or surgically into the mammary fat pad with the human breast cancer cell line MDA-MB-231. The developing tumors could then be treated with exogenous OSM, a neutralizing antibody to the OSM receptor β, a combination of the two treatments, or control treatments. Resulting data show that oncostatin M and the anti-OSMRβ neutralizing antibody appear to decrease tumor growth rates. Statistical analysis indicates however that differences seen are not significant. Further studies will help to elucidate how OSM contributes to tumor progression and metastasis through angiogenesis, cell detachment, and invasion.

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