title: RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells.
abstract: Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (Onco(Ad).RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. Onco(Ad).RGD-hTERT-EGFP had enhanced infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but little cytoxicity on normal urothelial SV-HUC-1 cells compared with the unmodified virus Onco(Ad).hTERT-EGFP. Notably, Onco(Ad).RGD-hTERT-TRAIL induced apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited xenograft initiation established by the oncolytic adenovirus-pretreated T24 sphere cells, and significantly suppressed tumor growth by intratumoral injection. These results provided a promising therapeutic strategy for CAR-negative bladder cancer through targeting CICs.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: J
authors.initials: J
authors.lastname: Xiao
authors.affiliation: College of Life Sciences, Northwest Agriculture and Forestry University, Yanglin 712100, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 1] State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: L
authors.initials: L
authors.lastname: Chu
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology; D009842:Oligopeptides / Q000235:genetics*; D050504:Oncolytic Viruses / Q000235:genetics*; D018874:Spheroids, Cellular / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039564:Integrin alphaV; D009842:Oligopeptides; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C047981:arginyl-glycyl-aspartic acid