Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway.
BMC Cancer. 2009 Dec 29;9:465. doi: 10.1186/1471-2407-9-465.
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.
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.
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.
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.
建立具有临床相关性的胶质母细胞瘤（GBM）动物模型仍然具有挑战性，许多常用的细胞系模型并不能重现患者 GBM 的浸润性生长模式。此前，我们曾报道过从人 GBM 中形成高度侵袭性肿瘤异种移植物的情况。然而，基于原发性组织建立肿瘤模型需要使这些模型能够充分标准化，具有始终保持高成功率的特点。
在这项工作中，我们从裸鼠异种移植的 29 份活检标本中收集了生长动力学数据，并对该模型进行了特征描述，重点是神经病理学和影像学特征。
异种移植 GBM 活检标本的肿瘤成功率为 96%，在体内随后的传代中接近 100%，而只有 4 个低级别肿瘤中有 1 个成功植入。从移植到出现症状的平均时间为 125 天 +/- 11.5 SEM。组织学上，原发异种移植物再现了母肿瘤的浸润特征，而内皮细胞增殖和坏死大多不存在。经过 4-5 次体内传代后，肿瘤变得更加血管化，出现坏死区，但也变得更加局限。MRI 通常在出现症状前几个月就显示与肿瘤生长相关的变化。
患者 GBM 活检标本的体内传代产生了具有代表性的肿瘤，具有高成功率和可重复的疾病过程。该模型提供了血管生成和浸润表型的组合，是体外增殖细胞系的良好替代品，可用于剖析脑肿瘤进展的机制。
