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 -catenin, MMP-16, snail and twist. Notably, the higher expression levels of -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 -catenin/MMP-16. J. Cell. Biochem. 116: 618-627, 2015. (c) 2014 Wiley Periodicals, Inc.
[1]Fourth Mil Med Univ, State Key Lab Canc Biol, Xian 710032, Peoples R China.
[2]Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp Digest Dis, Xian 710032, Peoples R China.
[3]Xiamen Univ, Affiliated Hosp 1, Dept Digest Dis, Xiamen 361003, Peoples R China.
[4]Xiamen Univ, Affiliated Hosp 1, Dept Pharm, Xiamen 361003, Peoples R China.
[5]Xiamen Univ, Affiliated Dongfang Hosp, Dept Med Oncol, Fuzhou 350000, Fujian, Peoples R China.
[6]KunMing Med Coll, Sch Stomatol, Dept Orthodont, Kunming 65000, Peoples R China.
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