Isolation and characterization of tumorspheres from a recurrent pineoblastoma patient: Feasibility of a patient-derived xenograft.
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.
Department of Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jiyong
J
Kwak
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jin-Kyoung
JK
Shim
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Dong Seok
DS
Kim
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ji-Hyun
JH
Lee
Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
Junjeong
J
Choi
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Junseong
J
Park
Department of Forensic Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kyoung-Jin
KJ
Shin
Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Se-Hoon
SH
Kim
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Pilnam
P
Kim
Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Yong-Min
YM
Huh
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Eui Hyun
EH
Kim
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jong Hee
JH
Chang
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sun Ho
SH
Kim
Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Seok-Gu
SG
Kang
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002648:Child; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation / Q000379:methods*; D010870:Pineal Gland / Q000473:pathology*; D010871:Pinealoma / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods*