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Open Access Highly Accessed Research article

A reproducible brain tumour model established from human glioblastoma biopsies

Jian Wang1*, Hrvoje Miletic12, Per Ø Sakariassen1, Peter C Huszthy1, Hege Jacobsen1, Narve Brekkå1, Xingang Li3, Peng Zhao3, Sverre Mørk2, Martha Chekenya1, Rolf Bjerkvig14 and Per Ø Enger15

Author Affiliations

1 Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway

2 Department of Pathology, University of Bergen, N-5021 Bergen, Norway

3 Qilu Hospital, Shandong University, 250013 Jinan, China

4 NorLux Neuro-Oncology, Centre Recherche de Public Santé, L-1150, Luxembourg

5 Department of Neurosurgery, Haukeland University Hospital, N-5021 Bergen, Norway

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BMC Cancer 2009, 9:465  doi:10.1186/1471-2407-9-465

Published: 29 December 2009

Abstract

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.