ALBA Synchrotron Light Source, Carrer de la Llum 2-26, 08290 Cerdanyola del Vallès, Barcelona, Spain.
The Translational Neurooncology Research Group, Department of Neurosurgery, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Anal Chem. 2022 Feb 1;94(4):1932-1940. doi: 10.1021/acs.analchem.1c02076. Epub 2021 Dec 29.
Glioblastoma multiforme (GBM) is the most aggressive brain tumor, characterized by short median survival and an almost 100% tumor-related mortality. The standard of care treatment for newly diagnosed GBM includes surgical resection followed by concomitant radiochemotherapy. The prevention of disease progression fails due to the poor therapeutic effect caused by the great molecular heterogeneity of this tumor. Previously, we exploited synchrotron radiation-based soft X-ray tomography and hard X-ray fluorescence for elemental microimaging of the shock-frozen GBM cells. The present study focuses instead on the biochemical profiling of live GBM cells and provides new insight into tumor heterogenicity. We studied bio-macromolecular changes by exploring the live-cell synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy in a set of three GBM cell lines, including the patient-derived glioblastoma cell line, before and after riluzole treatment, a medicament with potential anticancer properties. SR-FTIR microspectroscopy shows that GBM live cells of different origins recruit different organic compounds. The riluzole treatment of all GBM cell lines mainly affected carbohydrate metabolism and the DNA structure. Lipid structures and protein secondary conformation are affected as well by the riluzole treatment: cellular proteins assumed cross β-sheet conformation while parallel β-sheet conformation was less represented for all GBM cells. Moreover, we hope that a new live-cell approach for GBM simultaneous treatment and examination can be devised to target cancer cells more specifically, i.e., future therapies can develop more specific treatments according to the specific bio-macromolecular signature of each tumor type.
多形性胶质母细胞瘤(GBM)是最具侵袭性的脑肿瘤,其特点是中位生存期短,几乎 100%与肿瘤相关的死亡率。新诊断的 GBM 的标准治疗包括手术切除,然后进行同期放化疗。由于这种肿瘤的巨大分子异质性导致治疗效果不佳,疾病进展的预防失败。以前,我们利用同步辐射软 X 射线断层扫描和硬 X 射线荧光对冲击冷冻的 GBM 细胞进行元素微观成像。本研究则侧重于活 GBM 细胞的生化分析,并为肿瘤异质性提供新的见解。我们通过探索三组 GBM 细胞系(包括源自患者的胶质母细胞瘤细胞系)中的活细胞同步辐射傅里叶变换红外(SR-FTIR)微光谱,研究生物大分子的变化,这些细胞系在使用利鲁唑治疗前后,利鲁唑是一种具有潜在抗癌特性的药物。SR-FTIR 微光谱显示,不同来源的 GBM 活细胞募集不同的有机化合物。所有 GBM 细胞系的利鲁唑治疗主要影响碳水化合物代谢和 DNA 结构。脂质结构和蛋白质二级构象也受到利鲁唑治疗的影响:细胞蛋白呈交叉β-折叠构象,而所有 GBM 细胞的平行β-折叠构象较少。此外,我们希望为 GBM 设计一种新的活细胞联合治疗和检查方法,以更有针对性地靶向癌细胞,即未来的治疗方法可以根据每种肿瘤类型的特定生物大分子特征开发更具特异性的治疗方法。