IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway
Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-γ would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) deriv...
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doaj-1e592078cbdd4318992a2c1b0228b5da2020-11-24T20:57:55ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/318098318098IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL PathwayXinyuan Yang0Jingchun Du1Xia Xu2Chun Xu3Wu Song4Department of Gynecology and Obstetrics, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, ChinaKingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, ChinaKingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, ChinaKingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, ChinaDepartment of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 51800, ChinaMesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-γ would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-γ gene under the control of the EF1α promoter. The IFN-γ-modified MSCs effectively secreted functional IFN-γ, which led to long-term expression of TRAIL. More importantly, the IFN-γ-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-γ-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-γ-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-γ-modified MSCs.http://dx.doi.org/10.1155/2014/318098 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinyuan Yang Jingchun Du Xia Xu Chun Xu Wu Song |
spellingShingle |
Xinyuan Yang Jingchun Du Xia Xu Chun Xu Wu Song IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway Journal of Immunology Research |
author_facet |
Xinyuan Yang Jingchun Du Xia Xu Chun Xu Wu Song |
author_sort |
Xinyuan Yang |
title |
IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway |
title_short |
IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway |
title_full |
IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway |
title_fullStr |
IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway |
title_full_unstemmed |
IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway |
title_sort |
ifn-γ-secreting-mesenchymal stem cells exert an antitumor effect in vivo via the trail pathway |
publisher |
Hindawi Limited |
series |
Journal of Immunology Research |
issn |
2314-8861 2314-7156 |
publishDate |
2014-01-01 |
description |
Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-γ would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-γ gene under the control of the EF1α promoter. The IFN-γ-modified MSCs effectively secreted functional IFN-γ, which led to long-term expression of TRAIL. More importantly, the IFN-γ-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-γ-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-γ-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-γ-modified MSCs. |
url |
http://dx.doi.org/10.1155/2014/318098 |
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