Transforming growth factor-β1 induces bone marrow-derived mesenchymal stem cells to differentiate into cancer-associated fibroblasts.
- Author:
Lei SHANGGUAN
1
,
2
;
Email: SHANGGUANLEI@126.COM.
;
Xiaojie LI
3
;
Zhe WANG
3
;
Zhuojing LUO
3
Author Information
- Publication Type:Journal Article
- MeSH: Benzamides; pharmacology; Bone Marrow Cells; cytology; Cell Differentiation; drug effects; Cell Line, Tumor; Chemokine CXCL12; metabolism; Coculture Techniques; Culture Media, Conditioned; Dioxoles; pharmacology; Fibroblasts; cytology; Humans; Mesenchymal Stromal Cells; cytology; drug effects; Organic Chemicals; Receptors, CXCR4; metabolism; Recombinant Proteins; pharmacology; Smad3 Protein; metabolism; Transforming Growth Factor beta1; antagonists & inhibitors; pharmacology; Vimentin; metabolism
- From: Chinese Journal of Oncology 2015;37(11):804-809
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSMSCs 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.
RESULTSThe 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.
CONCLUSIONSTGF-β1 induces differentiation of local MSCs to CAFs by upregulating the expression of pSmad3, so as to further promote the growth of cancer cells.
