Apr 20th, 1:00 PM - Apr 19th, 4:00 PM
The Role of OSM in Breast Cancer Cell-Promoted Steoclastogenesis
Oncostatin M (OSM) is a pleiotropic cytokine in the interleukin (IL)-6 superfamily that functions in the immune system cascade, inflammation, cell proliferation, and cell mobility. OSM has been shown to inhibit the proliferation of breast cancer cells in vitro and was previously evaluated as a potential cancer therapy. Evidence from the literature and our preliminary data; however, suggest that OSM may promote metastasis of breast cancer cells and stimulate the formation of bone metastases. We have shown that OSM induces expression of several proteins known to participate in bone metastasis including proteinases, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) in human breast cancer cell lines. OSM has been shown to be a signaling molecule for osteoblast-mediated osteoclast differentiation, or osteoclastogenesis. To test whether OSM is also important in breast tumor cell-mediated osteoclastogenesis, we will utilize 66c14 and 4T1.2 mouse mammary tumor cells in a coculture system. The tumor cells will be cocultured with mouse bone marrow cells containing osteoclast progenitor cells for 9 days. The cocultures will be stained for osteoclasts with tartrate resistant acid phosphatase (TRAP), and TRAP+ cells will be counted. We predict that OSM will stimulate the formation of osteoclasts and that inhibiting OSM may have a positive effect on osteolytic breast cancer metastases. To date there have been no therapies developed that inhibit OSM to reduce osteolytic burden.