TY - JOUR
T1 - A reproducible brain tumour model established from human glioblastoma biopsies
AU - Wang, Jian
AU - Miletic, Hrvoje
AU - Sakariassen, Per T.
AU - Huszthy, Peter C.
AU - Jacobsen, Hege
AU - Brekkå, Narve
AU - Li, Xingang
AU - Zhao, Peng
AU - Mørk, Sverre
AU - Chekenya, Martha
AU - Bjerkvig, Rolf
AU - Enger, Per T.
N1 - Funding Information:
This work was supported by Helse-Vest, the Norwegian Cancer Society, the European Commission 6th Framework Program, Contract 504743, FUGE program (the Norwegian Research Council, project: 183258), and the National Natural Science Foundation of China (30672163). Technical assistance from Bodil Hansen and Tove Johansen is highly appreciated. Karen Egeland, Linda Vabø and Lene Nybø are gratefully acknowledged for taking care of the animals. We thank Anne Sidsel Herdlevær for assistance with photopraphy of whole tumour sections.
PY - 2009/12/29
Y1 - 2009/12/29
N2 - Background: Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates.Methods: In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features.Results: The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms.Conclusions: In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.
AB - Background: Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates.Methods: In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features.Results: The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms.Conclusions: In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.
UR - http://www.scopus.com/inward/record.url?scp=75649116753&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-9-465
DO - 10.1186/1471-2407-9-465
M3 - Article
C2 - 20040089
AN - SCOPUS:75649116753
SN - 1471-2407
VL - 9
JO - BMC Cancer
JF - BMC Cancer
M1 - 465
ER -