title: IFN-γ-primed human bone marrow mesenchymal stem cells induce tumor cell apoptosis in vitro via tumor necrosis factor-related apoptosis-inducing ligand.
abstract: Human mesenchymal stem cells hold promise as gene therapy vectors for delivery of various genes to solid tumors for either therapeutic or tumor-tracing purposes. However, whether Mesenchymal stem cells support or inhibit tumor growth remains unknown. Herein, we first observed that mesenchymal stem cells primed with IFN-γ selectively induced the death of tumor cell lines, but not normal cells. We further identified that IFN-γ-primed mesenchymal stem cells expressed tumor necrosis factor-related apoptosis-inducing ligand. Tumor-suppressive effect of IFN-γ-primed mesenchymal stem cells could be blocked by activity neutralization or expression reduction of tumor necrosis factor-related apoptosis-inducing ligand. Moreover, mesenchymal stem cells mediated apoptosis of tumor cells by activating caspase-3 in such cells, via a mechanism involving tumor necrosis factor-related apoptosis-inducing ligand. However, when IFN-γ-primed or non-primed mesenchymal stem cells were co-injected into nude mice along with H460 cells, tumor growth was much faster than that of the group receiving only tumor cells (p<0.01) because of the promoting vascularization effect of mesenchymal stem cells, although IFN-γ-primed mesenchymal stem cells also exerted a certain degree of tumor-suppressive effect compared with non-primed cells (2.79±0.9 g versus 2.03±0.6 g). Collectively, our findings show that IFN-γ-primed human mesenchymal stem cells could induce cancer cell apoptosis via TRAIL-mediated pathway. In addition, our data afford a novel explanation of the opposing effects of hMSCs presence on tumor growth in vitro and in vivo. Thus, more attention needs to be paid when seeking to exploit mesenchymal stem cells as a therapeutic option under the condition of malignant tumor.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, PR China.
authors.forename: Jingchun
authors.initials: J
authors.lastname: Du
authors.forename: Liwen
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Chen
authors.forename: Sunxing
authors.initials: S
authors.lastname: Yan
authors.forename: Ming
authors.initials: M
authors.lastname: Ke
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Lu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Weihua
authors.initials: W
authors.lastname: Yu
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma; D053148:Caspase 3