School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Maastricht Multimodal Molecular Imaging Institute, Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, 6229ER, The Netherlands.
Sci Rep. 2019 Feb 18;9(1):2205. doi: 10.1038/s41598-018-38257-0.
Treatment for medulloblastoma (MB) - the most common malignant pediatric brain tumor - includes prophylactic radiation administered to the entire brain and spine due to the high incidence of metastasis to the central nervous system. However, the majority of long-term survivors are left with permanent and debilitating neurocognitive impairments as a result of this therapy, while the remaining 30-40% of patients relapse with terminal metastatic disease. Development of more effective targeted therapies has been hindered by our lack of understanding of the underlying mechanisms regulating the metastatic process in this disease. To understand the mechanism by which MB metastasis occurs, three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) experiments were performed on whole brains from a mouse model of human medulloblastoma. Analyzing the tumor and surrounding normal brain in its entirety enabled the detection of low abundance, spatially-heterogeneous lipids associated with tumor development. Boundaries of metastasizing and non-metastasizing primary tumors were readily defined, leading to the identification of lipids associated with medulloblastoma metastasis, including phosphatidic acids, phosphatidylethanolamines, phosphatidylserines, and phosphoinositides. These lipids provide a greater insight into the metastatic process and may ultimately lead to the discovery of biomarkers and novel targets for the diagnosis and treatment of metastasizing MB in humans.
治疗髓母细胞瘤（MB）——最常见的小儿脑恶性肿瘤——包括对整个大脑和脊柱进行预防性辐射，因为这种肿瘤向中枢神经系统转移的发生率很高。然而，由于这种治疗，大多数长期存活者都存在永久性和使人虚弱的神经认知障碍，而其余 30-40%的患者则出现终末期转移性疾病复发。由于我们对调节这种疾病转移过程的潜在机制缺乏了解，因此开发更有效的靶向治疗方法受到了阻碍。为了了解 MB 转移发生的机制，对人髓母细胞瘤小鼠模型的整个大脑进行了三维基质辅助激光解吸/电离质谱成像（MALDI-MSI）实验。对肿瘤和周围正常大脑进行全面分析，能够检测到与肿瘤发展相关的低丰度、空间异质性脂质。很容易定义转移和非转移原发肿瘤的边界，从而确定与髓母细胞瘤转移相关的脂质，包括磷脂酸、磷脂酰乙醇胺、磷脂酰丝氨酸和磷酸肌醇。这些脂质为转移过程提供了更深入的了解，最终可能会发现用于诊断和治疗人类转移性 MB 的生物标志物和新靶点。
