title: Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro.
abstract: 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.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Wu-Gui
authors.initials: WG
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Fu-Zhou
authors.initials: FZ
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Hong-Kai
authors.initials: HK
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University Xinqiao Street, Chongqing 400037, China.
authors.forename: Tong-Wei
authors.initials: TW
authors.lastname: Chu
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis / Q000473:pathology; D010006:Osteoblasts / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C108639:SEMA3A protein, human; D040121:Semaphorin-3A
keywords: Breast cancer; bone metastases; osteoblastic differentiation; semaphorin 3A