Back to Search
Start Over
Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway.
- Source :
- PLoS ONE, Vol 7, Iss 12, p e52465 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.49ad5956f949beb740b4a783245aac
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0052465