Tissue Development and Evolution (TiDE) Division, Department of Laboratory Medicine, Lund University, SE22100 Lund, Sweden.
Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, SE22100 Lund, Sweden.
ACS Chem Neurosci. 2023 May 3;14(9):1602-1609. doi: 10.1021/acschemneuro.2c00776. Epub 2023 Apr 11.
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms.
多形性胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的脑肿瘤，对化疗和放疗高度耐受。GBM 与脂质含量的改变有关，但肿瘤细胞中的脂质代谢重编程尚未完全阐明。其中一个关键难题是定位与肿瘤生长和侵袭相关的脂质种类。更好地了解异常脂质代谢的定位及其脆弱性可能为新的治疗方法开辟道路。在这里，我们使用飞行时间二次离子质谱（ToF-SIMS）在两个具有不同组织病理学的 GBM 活检区域中对脂质组成进行空间探测：一个区域内大多数细胞具有均匀的大小和形状，称为同质部分，另一个区域内的细胞大小和形状差异很大，称为异质部分。我们的结果表明，同质部分中胆固醇、二酰基甘油和一些磷脂酰乙醇胺的水平升高，而异质部分则以各种脂肪酸、磷脂酰胆碱和磷脂酰肌醇为主。我们还观察到同质肿瘤区域中胆固醇的高表达与大细胞有关，但与巨噬细胞无关。我们的研究结果表明，ToF-SIMS 可以区分人类 GBM 肿瘤内不同部位的脂质分布，这与不同的分子机制有关。
