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

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...

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Bibliographic Details
Published in:Oncotarget 2016-07, Vol.7 (27), p.41294-41305
Main Authors: Zhou, Hai-Sen, Su, Xiao-Fang, Fu, Xing-Li, Wu, Guo-Zhong, Luo, Kun-Lun, Fang, Zheng, Yu, Feng, Liu, Hong, Hu, Hong-Juan, Chen, Liu-Sheng, Cai, Bing, Tian, Zhi-Qiang
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Animals
Cells, Cultured
Coculture Techniques
Epithelial-Mesenchymal Transition - drug effects
Humans
Male
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - physiology
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Pancreatic Neoplasms - pathology
Research Paper
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - pharmacology
Tumor Microenvironment - drug effects
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.9319