Tuesday, June 19, 2007 - 10:40 AM
Douglas Firs (Boise Centre on the Grove)

Breast Cancer Stimulation of Osteoclast Differentiation: The Role of Oncostatin M

Ken Tawara, Patrick Aranda, Sujatha Kadaba, Andrew Oler, and Cheryl L. Jorcyk. Boise State University, Boise, ID

Oncostatin M (OSM) is a pleiotropic cytokine in the interleukin (IL)-6 superfamily. OSM inhibits the proliferation of breast cancer cells in vitro and is therefore being evaluated as a potential cancer therapy. Evidence from the literature and our preliminary data; however, suggest that OSM may promote the formation of breast cancer bone metastases. OSM has been shown to promote osteoclast formation and enhance bone resorption by up-regulating proteins such as receptor activator of NF-ęB ligand (RANKL). In addition, we have demonstrated that OSM promotes the development of a metastatic phenotype in vitro and that OSM induces the expression of several proteins known to participate in bone resorption and bone metastasis, including proteinases, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). Thus far no studies have investigated OSM's role in bone metastasis and osteoclast differentiation. In order to investigate the effect of OSM on an in vitro model of breast cancer, we have co-cultured mouse bone marrow cells with mouse mammary cancer cells. Here we show that osteoclastogenesis is strongly stimulated by the presence of mammary cancer cells with the addition of OSM and RANKL. Additionally, we will co-culture mouse calvarie bone with mouse mammary cancer cells, to look for stimulation of osteolysis when OSM and RANKL are added. Thus far our findings suggest that OSM, in addition to RANKL, stimulates the formation of osteoclasts and the activity of these osteoclasts are expected to furthur increase with the additon of OSM and RANKL. NIH grant: P20RR16454