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PLoS One. 2012;7(12):e52465. doi: 10.1371/journal.pone.0052465. Epub 2012 Dec 20.

Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway.

Author information

1
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

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.

PMID:
23285052
PMCID:
PMC3527492
DOI:
10.1371/journal.pone.0052465
[Indexed for MEDLINE]
Free PMC Article
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