title: BM-MSCs promote prostate cancer progression via the conversion of normal fibroblasts to cancer-associated fibroblasts.
abstract: Recent studies have suggested that prostate cancer (PCa) is able to recruit bone marrow derived mesenchymal stem cells (BM-MSCs) to promote metastasis. The detailed mechanisms, especially the involvement of stromal cells, remain unclear. We found that the recruited BM-MSCs might be able to convert the normal fibroblasts to more cancer associated fibroblast (CAF)-like characteristics via alteration of secreted TGFβ-1. The consequences of such conversion might then enhance the PCa growth and invasion. Addition of functional TGFβ-1 or interruption with TGFβ-1 inhibitor SB431542 led to alteration of the BM-MSCs-induced CAF conversion and influence on the PCa cell growth and invasion. Together, these results suggest that BM-MSCs not only can be directly recruited by PCa epithelial cells to promote PCa invasion, they can also go through conversion of normal fibroblasts to CAFs to enhance PCa cell growth and invasion. Targeting the infiltrating BM-MSCs via either interruption of the interaction between PCa and BM-MSCs or prevention of the conversion of NFs to CAFs via inhibition of TGFβ-1 signal may result in the suppression of PCa progression.
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Simeng
authors.initials: S
authors.lastname: Wen
authors.affiliation: Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, Tianjin Medical University, Tianjin 300211, P.R. China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.affiliation: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018920:Coculture Techniques; D018450:Disease Progression; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1