RRC ID 48012
Author Yamaguchi S, Marumoto T, Nii T, Kawano H, Liao J, Nagai Y, Okada M, Takahashi A, Inoue H, Sasaki E, Fujii H, Okano S, Ebise H, Sato T, Suyama M, Okano H, Miura Y, Tani K.
Title Characterization of common marmoset dysgerminoma-like tumor induced by the lentiviral expression of reprogramming factors.
Journal Cancer Sci
Abstract Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c-MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma-like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma-like tumors were highly sensitive to DNA-damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c-MYC expression. These results indicate that DNA-damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c-MYC-targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC-based therapy.
Volume 105(4)
Pages 402-8
Published 2014-4-1
DOI 10.1111/cas.12367
PMID 24521492
PMC PMC4317795
MeSH Abnormal Karyotype Animals Callithrix Carcinogenesis / genetics* Dysgerminoma / genetics Dysgerminoma / pathology Dysgerminoma / therapy* Gene Expression Regulation, Neoplastic Humans Induced Pluripotent Stem Cells* Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / biosynthesis Kruppel-Like Transcription Factors / genetics Lentivirus Mice Octamer Transcription Factor-3 / biosynthesis Octamer Transcription Factor-3 / genetics Proto-Oncogene Proteins c-myc / biosynthesis Proto-Oncogene Proteins c-myc / genetics SOXB1 Transcription Factors / biosynthesis SOXB1 Transcription Factors / genetics Transduction, Genetic
IF 4.966
Times Cited 3
DNA material CSIV-CMV-MCS-IRES2-Venus (RDB08257)