Oncostatin M induction of vascular endothelial growth factor in human breast cancer cells promotes angiogenesis

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Oncostatin M (OSM), a pleiotropic cytokine belonging to the IL-6 family, is produced by many different cell types, including human T-lymphocytes, macrophages and monocytes. OSM has been shown to inhibit the proliferation of breast and other tumor cell lines in vitro and attention has been given to OSM as a potential cancer therapeutic. Recent studies, however, have shown that OSM may induce cell detachment and invasion in vitro, as well as the induction of Vascular Endothelial Growth Factor (VEGF) in endothelial and astroglioma cells. These results suggest that OSM may play a role in tumor progression and angiogenesis. We have demonstrated that OSM induces VEGF in several human breast cancer cell lines including MDA-MB-231, T47D, and MCF-7 and that this induction is dose and time dependent. To determine the role of OSM-induced VEGF in neovascularization in vitro, we utilized conditioned media taken from two separate human cancer cell lines, MDA-MB-231 and T47D, to investigate contributions to human umbilical vein endothelial cell (HUVEC) proliferation and subsequent tube formation. We show that OSM treated MDA-MB-231 breast cancer cell media increases HUVEC proliferation 78% over control, and increases HUVEC tube formation 57% in vitro. Assays to determine the in vivo effects of OSM-induced VEGF on neovascularization are currently under way. Our novel results show the first direct evidence that OSM-induced VEGF in human breast cancer has a potent pro-angiogenic effect on endothelial cells. These results suggest the importance of hindering OSM enhancement of angiogenesis during breast cancer progression and metastasis. This work was funded through NIH grant P20RR16454.