PMID- 25483835 OWN - NLM STAT- MEDLINE DCOM- 20150821 LR - 20181202 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 35 IP - 2 DP - 2015 Feb TI - Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells. PG - 367-75 LID - 10.3892/ijmm.2014.2019 [doi] AB - The inflammatory microenvironment contributes to cancer development and progression. Mesenchymal stem cells (MSCs), as important stromal cells, may be 'educated' by the inflammatory microenvironment to support the development of gastric cancer. Cytokines are a key component of cancer-related inflammation. Interleukin (IL)-6, as an inflammatory cytokine, has multiple roles in cancer. However, whether MSCs can be 'educated' by IL-6 to support gastric cancer remains unknown. In the present study, we focused on the phenotype and function of human umbilical cord-derived MSCs hUC‑MSCs pre-treated with IL-6 in gastric cancer. We found that the protein levels of alpha-smooth muscle actin (alpha-SMA) were upregulated, and phosphorylated nuclear factor (NF)-kappaB protein levels were downregulated in the hUC‑MSCs pre-treated with IL-6, as shown by western blot analysis. The levels of tumor‑promoting cytokines, including chemokine (C-C motif) ligand 5 (CCL5), platelet-derived growth factor‑BB (PDGF‑BB), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor alpha(TNFalpha), were markedly reduced in the hUC‑MSCs following treatment with IL-6, as shown by RT-qPCR. In in vitro experiments, we co-cultured MSCs with N-methyl‑N'‑nitro‑N‑nitrosoguanidine (MNNG)‑transformed GES-1 gastric epithelial cells or SGC-7901 gastric cancer cells. Transwell and colony-forming cell assays revealed that the hUC-MSCs significantly promoted gastric cellular migration and proliferation. However, following treatment with IL-6, the hUC-MSCs had no growth-promoting effect on the gastric epithelial cells and gastric cancer cells. In in vivo experiments, we co-transplanted MSCs and SGC-7901 cells into nude mice in order to establish a nude mouse model of gastric cancer. The hUC-MSCs significantly promoted the growth gastric tumors through the promotion of cell proliferation and the inhibition of cell apoptosis. On the contrary, pre-treatment with IL-6 provided the hUC‑MSCs with the ability to inhibit cell proliferation and significantly induce cell apoptosis. Taken together, our findings indicate that pre-treatment with IL-6 significantly abolishes the ability of hUC-MSCs to promote gastric epithelial cell proliferation and migration and provide new insight into the effects of the inflammatory cytokine, IL-6, on the tumor-promoting ability of MSCs and its role in gastric cancer. FAU - Wang, Mei AU - Wang M AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Cai, Jie AU - Cai J AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Huang, Feng AU - Huang F AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Zhu, Mengchu AU - Zhu M AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Zhang, Qiang AU - Zhang Q AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Yang, Tingting AU - Yang T AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Zhang, Xu AU - Zhang X AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Qian, Hui AU - Qian H AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. FAU - Xu, Wenrong AU - Xu W AD - Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, The Affiliated Hospital, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141202 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (ACTA2 protein, human) RN - 0 (Actins) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (Neoplasm Proteins) SB - IM MH - Actins/metabolism MH - Animals MH - Cell Line, Tumor MH - Coculture Techniques MH - Heterografts MH - Humans MH - Interleukin-6/*pharmacology MH - Mesenchymal Stem Cells/*metabolism/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - NF-kappa B/metabolism MH - Neoplasm Proteins/metabolism MH - Neoplasm Transplantation MH - Stomach Neoplasms/*metabolism/pathology MH - Umbilical Cord PMC - PMC4292781 EDAT- 2014/12/09 06:00 MHDA- 2015/08/22 06:00 PMCR- 2016/02/01 CRDT- 2014/12/09 06:00 PHST- 2014/06/27 00:00 [received] PHST- 2014/11/28 00:00 [accepted] PHST- 2014/12/09 06:00 [entrez] PHST- 2014/12/09 06:00 [pubmed] PHST- 2015/08/22 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - ijmm-35-02-0367 [pii] AID - 10.3892/ijmm.2014.2019 [doi] PST - ppublish SO - Int J Mol Med. 2015 Feb;35(2):367-75. doi: 10.3892/ijmm.2014.2019. Epub 2014 Dec 2.