Abstract
Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibition improved survival of nude mice and prevented osteolytic lesions resulting from tumor metastasis. Taken together, sclerostin promotes breast cancer cell migration, invasion and bone osteolysis. Inhibition of sclerostin may serve as an efficient strategy for interventions against breast cancer bone metastasis or osteolytic bone diseases.
Highlights
Breast cancer is the second leading cause of cancer-related deaths among women worldwide. 75–80% of patients with advanced disease develop bone metastasis[1, 2]
Sclerostin is up-regulated in tumor tissues derived from patients with breast cancer bone metastasis (BCBM)
Almost 80% of breast cancer patients have evidence of bone loss at baseline[15] and 65–75% of patients suffer from metastases to bone[16]
Summary
Breast cancer is the second leading cause of cancer-related deaths among women worldwide. 75–80% of patients with advanced disease develop bone metastasis[1, 2]. As an end-stage complication of breast cancer, bone metastasis frequently leads to detrimental skeletal-related events associated with significant morbidity[3,4,5]. The purpose of our study was to evaluate the expression level of sclerostin in tumor tissue derived from BCBM patients and explore its association with clinical outcome and tumor characteristics, including the presence of lytic bone disease. During multiple-steps of metastasis to bone, breast cancer cells successfully induce a sequence of changes, for instance, secreting cytokines to inhibit differentiation and maturation of osteoblasts whereas to enhance the activity of osteoclasts. We hypothesized that decreased sclerostin would suppress osteolytic bone lesions and reduce tumor burden, which may represent a target for inhibiting cancer-induced bone diseases and facilitating restoration of normal bone homeostasis
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