Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS).
Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS).
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DOI：
10.1007/s11060-015-2022-8
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发表时间：
2016-03
影响因子：
3.9
通讯作者：
Pannullo SC
中科院分区：
文献类型：
--
作者：
Chandra S;Parker DJ;Barth RF;Pannullo SC
多形性胶质母细胞瘤（GBM）是人类脑肿瘤中最致命的形式之一。这些肿瘤的浸润性生长模式包括在受完整血脑屏障保护的脑部分中，肿瘤细胞的个体和/或集群在距主要肿瘤块一定距离处扩散。GBM的病理生理学研究，可以大大提高了分析技术，能够在原位单细胞分辨率测量浸润肿瘤细胞。镁稳态是高级别胶质瘤的一个积极研究领域。在本研究中，我们使用了F98大鼠胶质瘤作为人类GBM的模型和二次离子质谱（西姆斯），CAMECA IMS-3f离子显微镜的元素/同位素成像技术，用于研究Mg分布与单细胞分辨率在冷冻干燥的脑组织冷冻切片。对主要肿瘤块、邻近脑组织中的肿瘤细胞和邻近正常脑中的浸润肿瘤细胞进行定量观察。脑组织含有4.70 ± 0.93 mmol/Kg湿重（平均值± SD）的显著较低的总Mg浓度，相比之下，主要肿瘤块的肿瘤细胞中的11.64 ± 1.96 mmol/Kg湿重和浸润性肿瘤细胞中的10.72 ± 1.76 mmol/Kg湿重（p<0.05）。单个肿瘤细胞的细胞核中含有升高水平的结合镁。这些观察结果表明，增强Mg-流入和Mg在肿瘤细胞中的结合增加，并为进一步研究GBM改变Mg稳态和激活Mg转运通道作为可能的治疗靶点提供了强有力的支持。
Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets.