TRAIL-Expressing Gingival-Derived Mesenchymal Stem Cells Inhibit Tumorigenesis of Tongue Squamous Cell Carcinoma
TRAIL-Expressing Gingival-Derived Mesenchymal Stem Cells Inhibit Tumorigenesis of Tongue Squamous Cell Carcinoma
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DOI：
10.1177/0022034514557815
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发表时间：
2015-01
影响因子：
7.6
通讯作者：
L. Xia;R. Peng;W. Leng;R. Jia;X. Zeng;X. Yang;M. Fan
中科院分区：
文献类型：
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作者：
L. Xia;R. Peng;W. Leng;R. Jia;X. Zeng;X. Yang;M. Fan
近年来的研究证实，来源于骨髓或脂肪组织的间充质干细胞（mesenchymal stromal/stem cells，MSCs）可以向多种肿瘤方向迁移。在这项研究中，我们探讨了人牙龈源性间充质干细胞（G-MSCs）是否可以向舌鳞状细胞癌（TSCC）迁移，并评估了工程G-MSCs表达和递送肿瘤坏死因子相关凋亡诱导配体（TRAIL）的抗肿瘤作用。用Transwell板进行的体外细胞迁移测定显示，人G-MSC可以向TSCC细胞系（Tca 8113和Cal 27）迁移。然后，人G-MSCs作为一种基于细胞的载体，通过慢病毒（LV）系统转导全长TRAIL和增强型绿色荧光蛋白报告基因（G-MSCs with full-length TRAIL; G-MSCFLT）。将Tca 8113和Cal 27分别与G-MSCFLT共培养，观察G-MSCFLT对肿瘤细胞的作用。这导致G-MSCFLT诱导大量肿瘤细胞坏死和凋亡。同时，通过将G-MSCFLT局部和系统地给予裸鼠（与肿瘤细胞混合注射和尾静脉注射）进行体内抗肿瘤试验。这表明G-MSCFLT可以减少甚至抑制TSCC的生长，无论给药方法如何，特别是当肿瘤细胞和G-MSCFLT以1：1的比例混合注射时，其显示没有肿瘤形成。进一步证实了G-MSCFLT向TSCC大量迁移。这些数据强调了G-MSC作为基于细胞的基因治疗的载体的有效性和表达TRAIL的G-MSC的抗肿瘤活性。
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.