Authors: Cheryl L. Jorcyk

Affiliation: Boise State University

Title: Breast cancer metastasis to bone

Abstract: Breast cancer is the seconding leading cause of cancer-related deaths in women in the United States.  Most cancers, including breast cancer, are lethal as a result of local invasion and the metastasis of cancer cells from the primary tumor to other tissues.  Approximately 80% of patients with metastatic breast cancer develop bone metastases, while liver or lung metastases affect approximately 25% of these patients.  Bone metastases are a significant source of morbidity, causing severe pain, pathologic fractures, bone deformity, hypercalcemia, and spinal cord compression.  Understanding the molecular determinants controlling the dissemination of breast cancer cells to bone could lead to more effective therapies that extend and improve the lives of patients. 

      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 breast cancer progression and metastasis to bone and other organs.  Previously, OSM was shown to promote osteoclast formation and enhance bone resorption by upregulating proteins such as receptor activator of NF-kB ligand (RANKL).  In our lab, we have demonstrated that OSM promotes the development of a metastatic phenotype in vitro and induces the expression of several proteins known to participate in bone resorption and bone metastasis, including proteinases, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF).  Thus far, no studies have investigated OSM's role in bone metastasis and osteoclast differentiation and activity.  Studies addressing these issues will be presented.  P20RR16454.