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Isolation and characterization of tumorspheres from a recurrent pineoblastoma patient: Feasibility of a patient-derived xenograft.

 Jiyong Kwak  ;  Jin-Kyoung Shim  ;  Dong Seok Kim  ;  Ji-Hyun Lee  ;  Junjeong Choi  ;  Junseong Park  ;  Kyoung-Jin Shin  ;  Se-Hoon Kim  ;  Pilnam Kim  ;  Yong-Min Huh  ;  Eui Hyun Kim  ;  Jong Hee Chang  ;  Sun Ho Kim  ;  Seok-Gu Ka 
 International Journal of Oncology, Vol.49(2) : 567-578, 2016 
Journal Title
 International Journal of Oncology 
Issue Date
Animals ; Brain Neoplasms/pathology* ; Child ; Feasibility Studies ; Humans ; Male ; Mice ; Neoplasm Transplantation/methods* ; Pineal Gland/pathology* ; Pinealoma/pathology* ; Transplantation, Heterologous/methods*
The existence of tumorspheres (TSs) might confer treatment resistance to pineoblastoma (PB). The existence of PB TSs with cellular immortalization potential has not yet been reported. We developed a procedure for isolating TSs from recurrent PB (rPB) and tested whether their properties made them suitable for use as a patient-derived xenograft (PDX). Immunocytochemical staining, RT-PCR and quantitative real-time PCR showed that, among stemness proteins, CD133, musashi and podoplanin were expressed at elevated levels in rPB TSs, but nestin was not. rPB TSs cultured under neuro-glial differentiation conditions expressed TUBB3, but not GFAP, MBP or NeuN. Unlike glioblastoma TSs, rPB TSs showed no clear evidence of invasion in 3D invasion assay or increased expression of genes associated with epithelial-mesenchymal transition. An orthotopic xenograft showed that tumor xenografts replicated the histopathological features of the patient tumor and expressed similar genome profiles, as determined by short tandem repeat genotyping. These data demonstrate the isolation and the characterization of rPB TSs for the first time. Using an orthotopic xenograft, we showed that rPB TSs could replicate the patient tumor, demonstrating their potential as a PDX for precision medicine.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Forensic Medicine (법의학과) > 1. Journal Papers
Yonsei Authors
강석구(Kang, Seok Gu) ORCID logo https://orcid.org/0000-0001-5676-2037
곽지용(Kwak, Jiyong) ORCID logo https://orcid.org/0000-0002-7738-9136
김동석(Kim, Dong Seok)
김선호(Kim, Sun Ho) ORCID logo https://orcid.org/0000-0003-0970-3848
김세훈(Kim, Se Hoon) ORCID logo https://orcid.org/0000-0001-7516-7372
김의현(Kim, Eui Hyun) ORCID logo https://orcid.org/0000-0002-2523-7122
신경진(Shin, Kyoung Jin) ORCID logo https://orcid.org/0000-0002-1059-9665
이지현(Lee, Ji Hyun)
장종희(Chang, Jong Hee)
허용민(Huh, Yong Min) ORCID logo https://orcid.org/0000-0002-9831-4475
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