Biggs Thelma, Foreman Janet, Sundstrom Lars, Regenass Urs, Lehembre Francois
Capsant Neurotechnologies, London, UK.
J Biomol Screen. 2011 Sep;16(8):805-17. doi: 10.1177/1087057111414895. Epub 2011 Aug 1.
Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor. Identification of new therapeutic regimens is urgently needed. A major challenge remains the development of a relevant in vitro model system with the necessary capacity and flexibility to profile compounds. The authors have developed and characterized a 3D culture system of brain cells (brain Hi-Spot) where GBM-derived cells can be incorporated (GBM/brain Hi-Spot). Immuno-fluorescence and electrophysiological recordings demonstrate that brain Hi-Spots recapitulate many features of brain tissue. Within this tissue, GBM-derived cell growth is monitored using a fluorescence assay. GBM-derived cells growing in Hi-Spots form tumor nodules that display properties of GBM such as 5-Ala positive staining, an acidic environment, and tumor-surrounding astrocyte activation. Temozolomide inhibits GBM growth in brain Hi-Spots, but it is not effective in 2D cultures. Other chemotherapeutics that have proven to be inefficient in GBM treatment display low activity against GBM-derived cells growing in brain Hi-Spots in comparison to their activity against GBM 2D cultures. These findings suggest that GBM/brain Hi-Spots represent a simple system to culture cells derived from brain tumors in an orthotopic environment in vitro and that the system is reliable to test GBM targeting compounds.
多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的原发性脑肿瘤类型。迫切需要鉴定新的治疗方案。一个主要挑战仍然是开发一种具有必要能力和灵活性来分析化合物的相关体外模型系统。作者开发并表征了一种脑细胞三维培养系统（脑高亮点），其中可以整合源自GBM的细胞（GBM/脑高亮点）。免疫荧光和电生理记录表明，脑高亮点概括了脑组织的许多特征。在该组织内，使用荧光测定法监测源自GBM的细胞生长。在高亮点中生长的源自GBM的细胞形成肿瘤结节，这些结节表现出GBM的特性，如5-丙氨酸阳性染色、酸性环境和肿瘤周围星形胶质细胞活化。替莫唑胺可抑制脑高亮点中的GBM生长，但在二维培养中无效。与它们对GBM二维培养的活性相比，其他已证明在GBM治疗中无效的化疗药物对在脑高亮点中生长的源自GBM的细胞显示出低活性。这些发现表明，GBM/脑高亮点代表了一种在体外原位环境中培养源自脑肿瘤的细胞的简单系统，并且该系统对于测试GBM靶向化合物是可靠的。
