title: Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) promote tumor growth by differentiating into carcinoma-associated fibroblasts (CAFs) and composing the tumor microenvironment. However, the mechanisms responsible for the transition of MSCs to CAFs are not well understood. Exosomes regulate cellular activities by mediating cell-cell communication. In this study, we aimed to investigate whether cancer cell-derived exosomes were involved in regulating the differentiation of human umbilical cord-derived MSCs (hucMSCs) to CAFs.
  
  
  RESULTS
  We first showed that gastric cancer cell-derived exosomes induced the expression of CAF markers in hucMSCs. We then demonstrated that gastric cancer cell-derived exosomes stimulated the phosphorylation of Smad-2 in hucMSCs. We further confirmed that TGF-β receptor 1 kinase inhibitor attenuated Smad-2 phosphorylation and CAF marker expression in hucMSCs after exposure to gastric cancer cell-derived exosomes.
  
  
  CONCLUSIONS
  Our results suggest that gastric cancer cells triggered the differentiation of hucMSCs to CAFs by exosomes-mediated TGF-β transfer and TGF-β/Smad pathway activation, which may represent a novel mechanism for MSCs to CAFs transition in cancer.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Gu
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Yan
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.forename: Chonghui
authors.initials: C
authors.lastname: Zhao
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Shi
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D004705:Endocytosis; D004789:Enzyme Activation; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases