title: Sendai virus-mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells.
abstract: Neuroblastoma (NB) is the most common extracranial solid tumor that originates from multipotent neural crest cells. NB cell populations that express embryonic stem cell-associated genes have been identified and shown to retain a multipotent phenotype. However, whether somatic reprogramming of NB cells can produce similar stem-cell like populations is unknown. Here, we sought to reprogram NB cell lines using an integration-free Sendai virus vector system. Of four NB cell lines examined, only SH-IN cells formed induced pluripotent stem cell-like colonies (SH-IN 4F colonies) at approximately 6 weeks following transduction. These SH-IN 4F colonies were alkaline phosphatase-positive. Array comparative genomic hybridization analysis indicated identical genomic aberrations in the SH-IN 4F cells as in the parental cells. SH-IN 4F cells had the ability to differentiate into the three embryonic germ layers in vitro, but rather formed NBs in vivo. Furthermore, SH-IN 4F cells exhibited resistance to cisplatin treatment and differentiated into endothelial-like cells expressing CD31 in the presence of vascular endothelial growth factor. These results suggest that SH-IN 4F cells are partially reprogrammed NB cells, and could be a suitable model for investigating the plasticity of aggressive tumors.
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: S M Rafiqul
authors.initials: SM
authors.lastname: Islam
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan.|Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suenaga
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takatori
authors.affiliation: Division of Business & Technology Development, DNAVEC Corporation, Tokyo, Japan.
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Division of Surgical Pathology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Hidetada
authors.initials: H
authors.lastname: Kawana
authors.affiliation: Division of Surgical Pathology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Itami
authors.affiliation: Laboratory of Cancer Genomics, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Sana
authors.initials: S
authors.lastname: Yokoi
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000066670:Cell Plasticity / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000166:cytology; D005822:Genetic Vectors / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000821:virology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000071317:Nanog Homeobox Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D029082:Sendai virus
chemical_list: D018398:Homeodomain Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D002945:Cisplatin
keywords: Induced pluripotent stem cells; Sendai virus; neuroblastoma; plasticity; reprogramming