Gastric Cancer Exosomes Trigger Differentiation of Umbilical Cord Derived Mesenchymal Stem Cells to Carcinoma-Associated Fibroblasts through TGF-β/Smad Pathway

被引：104

作者：

Gu, Jianmei ^{[1
]}

Qian, Hui ^{[1
]}

Shen, Li ^{[1
]}

Zhang, Xu ^{[1
]}

Zhu, Wei ^{[1
]}

Huang, Ling ^{[1
]}

Yan, Yongmin ^{[1
]}

Mao, Fei ^{[1
]}

Zhao, Chonghui ^{[1
]}

Shi, Yunyan ^{[1
]}

Xu, Wenrong ^{[1
,2
]}

机构：

[1] Jiangsu Univ, Sch Med Sci & Lab Med, Zhenjiang, Jiangsu, Peoples R China

[2] Jiangsu Univ, Affiliated Hosp, Dept Clin Lab Med, Zhenjiang, Jiangsu, Peoples R China

来源：

PLOS ONE | 2012年 / 7卷 / 12期

基金：

中国国家自然科学基金;

关键词：

PROMOTE TUMOR-GROWTH; TRANSITION;

D O I：

10.1371/journal.pone.0052465

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta 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-beta transfer and TGF-beta/Smad pathway activation, which may represent a novel mechanism for MSCs to CAFs transition in cancer.

引用

页数：8

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