title: TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells.
abstract: Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC(nsTRAIL) and MSC(stTRAIL). The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.
authors: Department of Surgery, University of British Columbia, Vancouver, Canada.
authors: M R
authors: MR
authors: Moniri
authors: X-Y
authors: XY
authors: Sun
authors: J
authors: J
authors: Rayat
authors: D
authors: D
authors: Dai
authors: Z
authors: Z
authors: Ao
authors: Z
authors: Z
authors: He
authors: C B
authors: CB
authors: Verchere
authors: L-J
authors: LJ
authors: Dai
authors: G L
authors: GL
authors: Warnock
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D000071063:Endoglin; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C497483:CD44 protein, human; D017077:Culture Media, Conditioned; C064206:ENG protein, human; D000071063:Endoglin; C491901:FAS protein, human; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019014:fas Receptor