PMID- 26498753 OWN - NLM STAT- MEDLINE DCOM- 20160818 LR - 20220330 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 15 DP - 2015 Oct 24 TI - Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness. PG - 793 LID - 10.1186/s12885-015-1780-1 [doi] LID - 793 AB - BACKGROUND: Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. METHODS: We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial- mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. RESULTS: The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, alpha-smooth muscle actin (alpha-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. CONCLUSIONS: Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer. FAU - Xue, Jianguo AU - Xue J AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Zhu, Yuan AU - Zhu Y AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Sun, Zixuan AU - Sun Z AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Ji, Runbi AU - Ji R AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Zhang, Xu AU - Zhang X AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Xu, Wenrong AU - Xu W AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. AD - The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, 212000, P. R. China. FAU - Yuan, Xiao AU - Yuan X AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Zhang, Bin AU - Zhang B AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Yan, Yongmin AU - Yan Y AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Yin, Lei AU - Yin L AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Xu, Huijuan AU - Xu H AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Zhang, Leilei AU - Zhang L AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Zhu, Wei AU - Zhu W AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. FAU - Qian, Hui AU - Qian H AD - Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P. R. China. lstmmmlst@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151024 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 SB - IM MH - Animals MH - Carcinogenesis/metabolism/pathology MH - Cell Line, Tumor MH - Cell Movement/*physiology MH - Cell Proliferation/*physiology MH - Cell Transformation, Neoplastic/*metabolism/pathology MH - Humans MH - Mesenchymal Stem Cells/*metabolism/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Neoplastic Stem Cells/*metabolism/pathology MH - Stomach Neoplasms/*metabolism/pathology MH - Xenograft Model Antitumor Assays/methods PMC - PMC4620013 EDAT- 2015/10/27 06:00 MHDA- 2016/08/19 06:00 PMCR- 2015/10/24 CRDT- 2015/10/27 06:00 PHST- 2015/02/11 00:00 [received] PHST- 2015/10/12 00:00 [accepted] PHST- 2015/10/27 06:00 [entrez] PHST- 2015/10/27 06:00 [pubmed] PHST- 2016/08/19 06:00 [medline] PHST- 2015/10/24 00:00 [pmc-release] AID - 10.1186/s12885-015-1780-1 [pii] AID - 1780 [pii] AID - 10.1186/s12885-015-1780-1 [doi] PST - epublish SO - BMC Cancer. 2015 Oct 24;15:793. doi: 10.1186/s12885-015-1780-1.