Human MSCs promotes colorectal cancer epithelial-mesenchymal transition and progression via CCL5/β-catenin/Slug pathway

被引：68

作者：

Chen, Ke ^{[1
]}

Liu, Qianqian ^{[1
]}

Tsang, Lai Ling ^{[2
]}

Ye, Qiao ^{[1
]}

Chan, Hsiao Chang ^{[2
,3
]}

Sun, Yunwei ^{[1
]}

Jiang, Xiaohua ^{[2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Rui Jin Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China

[2] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med,Epithelial Cell Biol Res Ctr, Key Lab Regenerat Med,Minist Educ, Hong Kong, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Shenzhen Res Inst, Sch Biomed Sci, Core Lab, Room 409A, Shenzhen 518057, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

STEM-CELLS; TUMOR PROGRESSION; COLON-CANCER; CHEMOKINE CCL5; EXPRESSION; RANTES; MICROENVIRONMENT; DIFFERENTIATION; TRANSCRIPTION; METASTASIS;

D O I：

10.1038/cddis.2017.138

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-alpha-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion. TNF-alpha-primed-hMSCs secrete high level of CCL5, which interacts with its receptor CCR1 expressed in colon cancer cells. Interestingly, the stimulation of colon cancer cell progression by TNF-alpha-primed hMSCs is associated with the upregulation of beta-catenin signaling pathway. Blocking beta-catenin pathway significantly decreases the TNF-alpha-primed-conditioned medium or CCL5-mediated cancer cell progression by decreasing the enhancement of Slug, suggesting that the CCL5/beta-catenin/Slug pathway plays a critical role in hMSC-mediated cancer progression. Furthermore, in vivo model in nude mice confirms the ability of hMSCs to promote the proliferation and progression of colon cancer cells, and the upregulation of CCl5/beta-catenin/Slug pathway. Taken together, the present study has demonstrated a novel pathway involving CCl5/CCR1/beta-catenin/Slug, via which hMSCs promotes CRC development.

引用

页码：e2819 / e2819

页数：12

共 51 条

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