Molecular Regulators of Bone Sialoprotein Expression in Human Metastatic Breast Cancer Cells

Introduction Death from cancer is usually due to the development of metastases, and the skeleton is the organ most frequently involved. Clinically, skeletal metastases are a frequently encountered event. The patient develops pain, pathologic fractures, hypercalcemia, and spinal cord compression and experiences an inexorable decline in mobility and quality of life. Recent reports have demonstrated a clinical correlation between the expression of the bone related extracellular matrix molecule, bone sialoprotein (BSP) in primary breast cancer lesions and the preferential metastasis to bone (1-3). BSP expression was found to be a poor prognostic sign when present in the primary lesion and there was a significantly increased incidence of subsequent bone metastases in patients who expressed higher levels of BSP. Additionally, it has been demonstrated that bone metastases from breast and prostate cancers express elevated levels of BSP compared to visceral metastases (4). Given the correlation between BSP expression in these malignancies and the subsequent metastasis to bone, we hypothesize that the molecular regulators of ectopic BSP expression in these cancers play important roles in the preferential metastasis to bone. In order to begin to test this hypothesis, we have used a combination of electromobility shift assays and promoter-reporter expression studies to identify the molecular regulators of BSP expression in metastatic breast cancer cells.