title: IFN-γ-secreting-mesenchymal stem cells exert an antitumor effect in vivo via the TRAIL pathway.
abstract: 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.
authors: Department of Gynecology and Obstetrics, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Xinyuan
authors: X
authors: Yang
authors: Kingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, China.
authors: Jingchun
authors: J
authors: Du
authors: Kingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, China.
authors: Xia
authors: X
authors: Xu
authors: Kingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, China.
authors: Chun
authors: C
authors: Xu
authors: Department of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 51800, China.
authors: Wu
authors: W
authors: Song
mesh_terms: D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D060846:Cell Engineering; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004789:Enzyme Activation; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007371:Interferon-gamma / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D007371:Interferon-gamma; D053148:Caspase 3