Sclerostin inhibition alleviates breast cancer-induced bone metastases and muscle weakness.

ABSTRACT: Breast cancer bone metastases often cause a debilitating non-curable condition with osteolytic lesions, muscle weakness and a high mortality. Current treatment comprises chemotherapy, irradiation, surgery and anti-resorptive drugs that restrict but do not revert bone destruction. In metastatic breast cancer cells, we determined the expression of sclerostin, a soluble Wnt inhibitor that represses osteoblast differentiation and bone formation. In mice with breast cancer bone metastases, pharmacological inhibition of sclerostin using an anti-sclerostin antibody (Scl-Ab) reduced metastases without tumor cell dissemination to other distant sites. Sclerostin inhibition prevented the cancer-induced bone destruction by augmenting osteoblast-mediated bone formation and reducing osteoclast-dependent

SUBMITTER: Hesse E 

PROVIDER: S-EPMC6538320 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature