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Chinese Journal of Oncology ; (12): 804-809, 2015.
Article Dans Chinois | WPRIM | ID: wpr-286719

Résumé

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>


Sujets)
Humains , Benzamides , Pharmacologie , Cellules de la moelle osseuse , Biologie cellulaire , Différenciation cellulaire , Lignée cellulaire tumorale , Chimiokine CXCL12 , Métabolisme , Techniques de coculture , Milieux de culture conditionnés , Dioxoles , Pharmacologie , Fibroblastes , Biologie cellulaire , Cellules souches mésenchymateuses , Biologie cellulaire , Composés chimiques organiques , Récepteurs CXCR4 , Métabolisme , Protéines recombinantes , Pharmacologie , Protéine Smad-3 , Métabolisme , Facteur de croissance transformant bêta-1 , Pharmacologie , Vimentine , Métabolisme
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