A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo.
Limited availability of in vitro and in vivo model systems has hampered efforts to understand tumor biology and test novel therapies for ependymoma, the third most common malignant brain tumor that occurs in children. To develop clinically relevant animal models of ependymoma, we directly injected a fresh surgical specimen from a 9-year-old patient into the right cerebrum of RAG2/severe complex immune deficiency (SCID) mice. All five mice receiving the initial transplantation of the patient tumor developed intracerebral xenografts, which have since been serially subtransplanted in vivo in mouse brains for 4 generations and can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors shared nearly identical histopathological features with the original tumors, harbored 8 structural chromosomal abnormalities as detected with spectral karyotyping, maintained gene expression profiles resembling that of the original patient tumor with the preservation of multiple key genetic abnormalities commonly found in human ependymomas, and contained a small population (<2.2%) of CD133(+) stem cells that can form neurospheres and display multipotent capabilities in vitro. The permanent cell line (BXD-1425EPN), which was derived from a passage II xenograft tumor and has been passaged in vitro more than 70 times, expressed similar differentiation markers of the xenograft tumors, maintained identical chromosomal abnormalities, and formed tumors in the brains of SCID mice. In conclusion, direct injection of primary ependymoma tumor cells played an important role in the generation of a clinically relevant mouse model IC-1425EPN and a novel cell line, BXD-1425EPN. This cell line and model will facilitate the biological studies and preclinical drug screenings for pediatric ependymomas.
Laboratory of Molecular Neuro-Oncology, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin Street, MC 3-3320, Houston, TX 77030, USA.
Litian
L
Yu
Patricia A
PA
Baxter
Horatiu
H
Voicu
Sivashankarappa
S
Gurusiddappa
Yijue
Y
Zhao
Adekunle
A
Adesina
Tsz-Kwong
TK
Man
Qin
Q
Shu
Yu-Jing
YJ
Zhang
Xiu-Mei
XM
Zhao
Jack M
JM
Su
Lazlo
L
Perlaky
Robert
R
Dauser
Murali
M
Chintagumpala
Ching C
CC
Lau
Susan M
SM
Blaney
Pulivarthi H
PH
Rao
Hon-Chiu Eastwood
HC
Leung
Xiao-Nan
XN
Li
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D004806:Ependymoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*