TRAIL-Expressing Gingival-Derived Mesenchymal Stem Cells Inhibit Tumorigenesis of Tongue Squamous Cell Carcinoma

作者：Linjian Xia, Rui Peng, Wei‐Dong Leng, Rong Jia, Xiao‐Hua Zeng, Xu Yang, Mengyuan Fan · 发表于：Journal of Dental Research · 年份：2014 · DOI：10.1177/0022034514557815 · 被引用次数：32 · 研究领域：Mesenchymal stem cell research、Cancer Research and Treatments、Virus-based gene therapy research

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 dat...