Sendai virus‐mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells

Cancer Science

S. M. Rafiqul Islam¹  Yusuke Suenaga¹  Atsushi Takatori¹  Yasuji Ueda²  Yoshiki Kaneko¹  Hidetada Kawana⁴  Makiko Itami⁴  Miki Ohira⁵  Sana Yokoi³ 

[1] Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, Chiba, Japan;Division of Business & Technology Development, DNAVEC Corporation, Tokyo, Japan;Cancer Genome Center, Chiba Cancer Center Research Institute, Chiba, Japan;Division of Surgical Pathology, Chiba Cancer Center, Chiba, Japan;Laboratory of Cancer Genomics, Chiba Cancer Center Research Institute, Chiba, Japan

关键词: Induced pluripotent stem cells;    neuroblastoma;    plasticity;    reprogramming;    Sendai virus;   

DOI  :  10.1111/cas.12746

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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