title: [Transforming growth factor-β1 induces bone marrow-derived mesenchymal stem cells to differentiate into cancer-associated fibroblasts].
abstract: OBJECTIVE
  To investigate the effect of transforming growth factor-β1 (TGF-β1) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into cancer-associated fibroblasts(CAFs).
  
  
  METHODS
  MSCs were cultured in α-MEM with recombinant human TGF-β1 or in tumor-conditioned medium.The expression of CAFs markers were detected by immunofluorescence and quantitative RT-PCR.
  
  
  RESULTS
  The qRT-PCR assay showed that the expression of CAFs markers FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin were 9.92±2.16, 7.76±1.28, 3.04±0.95, 3.28±2.16, 2.13±0.71, 1.41±0.66, 2.25±0.86 and 1.38±0.56, respectively, significantly upregulated in the MSCs co-cultured with TGF-β1 or TCM. The relative levels of FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin mRNA in the TCM group were 7.52±1.76, 5.02±1.18, 1.98±1.19, 1.82±1.19, 2.95±0.86, 1.44±0.67, 2.08±0.74 and 1.47±0.55, respectively, indicating that MSCs can express CAFs phenotype.TGF beta signaling pathway inhibitor SB-431542 could inhibit the differentiation. Both immunofluorescence and Western blot confirmed the above results.
  
  
  CONCLUSIONS
  TGF-β1 induces differentiation of local MSCs to CAFs by upregulating the expression of pSmad3, so as to further promote the growth of cancer cells.
authors.affiliation: Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China; Email: shangguanlei@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shangguan
authors.affiliation: Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhuojing
authors.initials: Z
authors.lastname: Luo
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004149:Dioxoles / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D009930:Organic Chemicals; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D004149:Dioxoles; D009930:Organic Chemicals; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C420642:alpha minimal essential medium