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Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness

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...

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Autores principales: Xue, Jianguo, Zhu, Yuan, Sun, Zixuan, Ji, Runbi, Zhang, Xu, Xu, Wenrong, Yuan, Xiao, Zhang, Bin, Yan, Yongmin, Yin, Lei, Xu, Huijuan, Zhang, Leilei, Zhu, Wei, Qian, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620013/
https://www.ncbi.nlm.nih.gov/pubmed/26498753
http://dx.doi.org/10.1186/s12885-015-1780-1
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author Xue, Jianguo
Zhu, Yuan
Sun, Zixuan
Ji, Runbi
Zhang, Xu
Xu, Wenrong
Yuan, Xiao
Zhang, Bin
Yan, Yongmin
Yin, Lei
Xu, Huijuan
Zhang, Leilei
Zhu, Wei
Qian, Hui
author_facet Xue, Jianguo
Zhu, Yuan
Sun, Zixuan
Ji, Runbi
Zhang, Xu
Xu, Wenrong
Yuan, Xiao
Zhang, Bin
Yan, Yongmin
Yin, Lei
Xu, Huijuan
Zhang, Leilei
Zhu, Wei
Qian, Hui
author_sort Xue, Jianguo
collection PubMed
description 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, α-smooth muscle actin (α-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-46200132015-10-26 Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness Xue, Jianguo Zhu, Yuan Sun, Zixuan Ji, Runbi Zhang, Xu Xu, Wenrong Yuan, Xiao Zhang, Bin Yan, Yongmin Yin, Lei Xu, Huijuan Zhang, Leilei Zhu, Wei Qian, Hui BMC Cancer Research Article 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, α-smooth muscle actin (α-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1780-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-24 /pmc/articles/PMC4620013/ /pubmed/26498753 http://dx.doi.org/10.1186/s12885-015-1780-1 Text en © Xue et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Xue, Jianguo
Zhu, Yuan
Sun, Zixuan
Ji, Runbi
Zhang, Xu
Xu, Wenrong
Yuan, Xiao
Zhang, Bin
Yan, Yongmin
Yin, Lei
Xu, Huijuan
Zhang, Leilei
Zhu, Wei
Qian, Hui
Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title_full Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title_fullStr Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title_full_unstemmed Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title_short Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
title_sort tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620013/
https://www.ncbi.nlm.nih.gov/pubmed/26498753
http://dx.doi.org/10.1186/s12885-015-1780-1
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