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.
The Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Hospital and School of Stomatology, Wuhan University, Wuhan, China Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
L
L
Xia
The Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Hospital and School of Stomatology, Wuhan University, Wuhan, China.
R
R
Peng
Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
W
W
Leng
The Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Hospital and School of Stomatology, Wuhan University, Wuhan, China.
R
R
Jia
Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
X
X
Zeng
Department of Endodontics, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
X
X
Yang
The Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Hospital and School of Stomatology, Wuhan University, Wuhan, China fmwwhu@163.com xyang.gmu@gmail.com.
M
M
Fan
D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D060846:Cell Engineering; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics; D005881:Gingiva / Q000166:cytology* / Q000502:physiology; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D010012:Osteogenesis / Q000502:physiology; D011897:Random Allocation; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000235:genetics*; D014062:Tongue Neoplasms / Q000473:pathology* / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
TNF-related apoptosis-inducing ligand; cell migration assays; gene therapy; nude mice; transfection; vehicles