Journal
ONCOTARGET
Volume 7, Issue 27, Pages 41294-41305Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9319
Keywords
mesenchymal stem cells; pancreatic adenocarcinoma; epithelial-mesenchymal transition; transforming growth factor-beta 1
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Funding
- Science and Technology Project Foundation of Nanjing [201303032]
- Medical Science and Technology Development Foundation of Jiangsu University [JLY20140160]
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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-a and IFN-Y 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-a and IFN-Y 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-a and IFN-Y provoked expression transforming growth factor-beta 1 (TGF-beta 1). MSCs promoting EMT-mediated PA cells invasion could be reversed by short interfering RNA of TGF-beta 1. 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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