TRAIL-expressing gingival-derived mesenchymal stem cells inhibit tumorigenesis of tongue squamous cell carcinoma.
Recent research has verified that mesenchymal stromal/stem cells (MSCs) derived from bone marrow or adipose tissues can migrate toward a variety of tumors. In this study, we explored whether human gingival-derived MSCs (G-MSCs) can migrate toward tongue squamous cell carcinoma (TSCC) and evaluated the antitumor effect of engineered G-MSCs in expressing and delivering the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). An in vitro cell migration assay with Transwell plates showed that human G-MSCs can migrate toward TSCC cell lines (Tca8113 and Cal27). Then, human G-MSCs, as a type of cell-based vehicle, were transduced with full-length TRAIL and enhanced green fluorescent protein reporter genes by the lentivirus (LV) system (G-MSCs with full-length TRAIL; G-MSCFLT). Tca8113 and Cal27 were co-cultured with G-MSCFLT, respectively, to evaluate the function of G-MSCFLT on tumor cells in vitro. This resulted in G-MSCFLT's inducing a great number of tumor cell necrosis and apoptosis. Meanwhile, in vivo antitumor assays were performed by administering G-MSCFLT to nude mice locally and systematically (mixed injection with tumor cells and tail vein injection). This showed that G-MSCFLT can reduce or even inhibit TSCC growth regardless of the method of administration, especially when the mixed injection of tumor cells and G-MSCFLT was at a ratio of 1:1, which showed no tumor formation. Furthermore, this verified that G-MSCFLT migrated toward TSCC in quantity. These data emphasize the effectiveness of G-MSCs as a vehicle for cell-based gene therapy and the antitumor activity of TRAIL-expressing G-MSCs.
['Xia|L|L|', 'Peng|R|R|', 'Leng|W|W|', 'Jia|R|R|', 'Zeng|X|X|', 'Yang|X|X|', 'Fan|M|M|']
D050156:Adipogenesis D000818:Animals D017209:Apoptosis D063646:Carcinogenesis D002294:Carcinoma, Squamous Cell D018929:Cell Culture Techniques D002454:Cell Differentiation D060846:Cell Engineering D045744:Cell Line, Tumor D002465:Cell Movement D018920:Coculture Techniques D005818:Genetic Engineering D005822:Genetic Vectors D005881:Gingiva D006801:Humans D016086:Lentivirus D059630:Mesenchymal Stem Cells D051379:Mice D008819:Mice, Nude D009336:Necrosis D010012:Osteogenesis D011897:Random Allocation D011994:Recombinant Proteins D053221:TNF-Related Apoptosis-Inducing Ligand D014062:Tongue Neoplasms D023041:Xenograft Model Antitumor Assays
cell migration assays vehicles nude mice gene therapy TNF-related apoptosis-inducing ligand transfection