Oncotarget

Research Papers:

Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-β1 induced epithelial-mesenchymal transition

Hai-Sen Zhou, Xiao-Fang Su, Xing-Li Fu, Guo-Zhong Wu, Kun-Lun Luo, Zheng Fang, Feng Yu, Hong Liu, Hong-Juan Hu, Liu-Sheng Chen, Bing Cai and Zhi-Qiang Tian _

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Oncotarget. 2016; 7:41294-41305. https://doi.org/10.18632/oncotarget.9319

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Abstract

Hai-Sen Zhou2,*, Xiao-Fang Su3,*, Xing-Li Fu4,*, Guo-Zhong Wu5, Kun-Lun Luo5, Zheng Fang5, Feng Yu5, Hong Liu5, Hong-Juan Hu2, Liu-Sheng Chen2, Bing Cai1, Zhi-Qiang Tian1,5

1Department of General Surgery, Wuxi People’s Hospital, Nanjing Medical University, Wuxi 214023, P.R. China

2Nanjing Lishui People’s Hospital, Nanjing 211200, P.R. China

3Department of Rehabilitation Medicine, The 101st Hospital of Chinese PLA, Wuxi 214044, P.R. China

4Health Science Center, Jiangsu University, Zhenjiang 212013, P.R. China

5Department of General Surgery, The 101st Hospital of Chinese PLA, Wuxi 214044, P.R. China

*These authors are contributed equally to this work

Correspondence to:

Zhi-Qiang Tian, email: zhiqiangtiann@163.com

Bing Cai, email: caibing@wuxiph.com

Keywords: mesenchymal stem cells, pancreatic adenocarcinoma, epithelial-mesenchymal transition, transforming growth factor-β1

Received: December 28, 2015     Accepted: April 25, 2016     Published: May 12, 2016

ABSTRACT

Mesenchymal stem cells (MSCs) could be ideal delivery vehicles for antitumor biological agents in pancreatic adenocarcinoma (PA). While the role of MSCs in tumor growth is elusive. Inflammation is an important feature of PA. In this study, we reported that MSCs pre-stimulated with the combination of TNF-α and IFN-γ promote PA cells invasion. The invasion of PA cell lines were evaluate by wound healing assay and transwell assay in vitro and liver metastasis in nude mice. We observed MSCs pre-stimulated with the combination of TNF-α and IFN-γ promoted PA cells invasion in vitro and in vivo. Consistent with MSCs promoting PA cells invasion, PA cells were found undergo epithelial-mesenchymal transition (EMT). We demonstrated that MSCs pre-stimulated with both of TNF-α and IFN-γ provoked expression transforming growth factor-β1 (TGF-β1). MSCs promoting EMT-mediated PA cells invasion could be reversed by short interfering RNA of TGF-β1. Our results suggest that MSCs could promote PA cells invasion in inflammation microenvironment and should be cautious as delivery vehicles in molecular target therapy.


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