Tuesday, June 19, 2007 - 11:00 AM Douglas Firs (Boise Centre on the Grove) 330
Oncostatin M Induces VEGF through HIF-1α
David Chang, Boise State University, Boise, ID
Oncostatin M (OSM) is a multifunctional, IL-6 type cytokine that exhibits both pro- and anti-inflammatory effects. OSM has been shown to inhibit the proliferation of breast and other tumor cell lines in vitro and has been suggested as a potential cancer therapeutic. Other studies have provided evidence that OSM plays a promotional role in tumor progression through stimulation of cell detachment and invasion in vitro and induction of vascular endothelial growth factor (VEGF) in endothelial and astroglioma cells. We have shown that OSM induces VEGF by approximately 4-fold in human breast cancer cell lines in a dose- and time-dependent manner. Conditioned media from OSM-treated breast cancer cells causes a 12-fold increase in neovascularization in an in vivo Matrigel plug assay. Additionally, here we demonstrate a novel property of OSM in the upregulation of hypoxia-inducible factor-1 alpha (HIF1ƒα), a potent pro-angiogenic transcription factor. This induction by OSM is seen by 4 hours and peaks at 24 hours. Our results give direct evidence that OSM-induced VEGF in human breast cancer cells occurs through activation of HIF1ƒα. NIH grant P20RR16454.