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Mesenchymal Stem Cells Promote Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer Though Paracrine Cues and Close Physical Contact
Author(s) -
Xue Zengfu,
Wu Xiumin,
Chen Xiong,
Liu Yali,
Wang Xin,
Wu Kaichun,
Nie Yongzhan,
Fan Daiming
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25013
Subject(s) - paracrine signalling , mesenchymal stem cell , epithelial–mesenchymal transition , metastasis , microbiology and biotechnology , cancer cell , cancer stem cell , cancer metastasis , cancer research , cancer , chemistry , biology , stem cell , medicine , receptor , biochemistry
Mesenchymal stem cells (MSCs) have been shown to integrate into the tumor stroma; however, the precise mechanisms of this process are still elusive. In this study, the EMT phenotype and the enhanced metastatic ability of tumor cells were observed using transwell and trans‐endothelial migration assays, respectively, as well as by using electron and laser confocal microscopy. Critical genes were screened and validated using gene arrays and clinical samples, and the changes at the protein level were examined both in vitro and in vivo. Cancer cells acquired an “activated” carcinoma‐associated fibroblasts (CAFs) phenotype after being in close contact with MSCs and enhancing tumor metastasis and growth in vivo. Paracrine signals also induced EMT and promoted transwell and trans‐endothelial migration, the changes were dependent on β‐catenin, MMP‐16, snail and twist. Notably, the higher expression levels of β‐catenin and MMP‐16 were correlated with tumor invasion and distant organ and lymph node metastases in intestinal type gastric cancer. MSCs within the tumor niche significantly facilitated tumor growth and metastasis by paracrine cues and close physical connection. This occurred partly through snail, twist and its downstream targets, specifically β‐catenin/MMP‐16. J. Cell. Biochem. 116: 618–627, 2015. © 2014 Wiley Periodicals, Inc.