Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro

Breast cancer bone metastases are attributed to multiple cellular and molecular interactions between the cancer cells and the bone microenvironment. Some breast cancers (about 10%) manifest predominant osteoblastic bone metastases. However, the effects of cancer cell-produced factors on osteoblastic differentiation are not fully understood. Semaphorin 3A (Sema 3A) is a newly identified regulatory factor of bone rebuilding. In the present study, we demonstrated that human breast cancer MCF-7 cells, which preferentially form osteoblastic bone metastases, exhibited increased Sema 3A expression levels. We also found that MCF-7 cell-derived Sema 3A stimulated osteoblastic differentiation and nuclear β-catenin accumulation, and these effects could be blocked by shRNA Sema 3A or a Sema 3A-neutralizing antibody. In conclusion, our data suggest that MCF-7 cell-derived Sema 3A plays a causative role in osteoblastic bone metastases progression by stimulating osteoblastic differentiation.