title: Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.
abstract: BACKGROUND
  Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A.
  
  
  METHODS
  We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation.
  
  
  RESULTS
  Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished β-catenin expression in osteogenitor MC3T3-E1 cells.
  
  
  CONCLUSIONS
  Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the β-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Fuzhou
authors.initials: F
authors.lastname: Liu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shen
authors.forename: Hao
authors.initials: H
authors.lastname: Qiu
authors.forename: Xu
authors.initials: X
authors.lastname: Hu
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Tongwei
authors.initials: T
authors.lastname: Chu
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D003470:Culture Media; D015536:Down-Regulation; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D040121:Semaphorin-3A / Q000378:metabolism*
chemical_list: D003470:Culture Media; D040121:Semaphorin-3A
keywords: Osteoblastic differentiation; Prostate cancer; Semaphorin 3A