Mass Spectrometry Imaging Reveals Abnormalities in Cardiolipin Composition and Distribution in Astrocytoma Tumor Tissues.
Mass Spectrometry Imaging Reveals Abnormalities in Cardiolipin Composition and Distribution in Astrocytoma Tumor Tissues.
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DOI：
10.3390/cancers15102842
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发表时间：
2023-05-19
期刊：
影响因子：
5.2
通讯作者：
Eberlin, Livia S. S.
中科院分区：
文献类型：
--
作者：
Krieger, Anna C. C.;Macias, Luis A. A.;Goodman, J. Clay;Brodbelt, Jennifer S. S.;Eberlin, Livia S. S.
心磷脂是细胞器和细胞能量产生的重要线粒体脂质。在胶质瘤异种移植模型中发现心磷脂的丰度和多样性发生了变化。在这里，我们利用质谱学成像技术，在组织学不同的肿瘤微环境中绘制出人类正常和星形细胞瘤中心磷脂的变化。在肿瘤组织中检测到的较长链心磷脂物种的相对丰度明显低于正常皮质。心磷脂的多样性与肿瘤微环境中的组织学趋势相关，包括肿瘤细胞侵袭和肿瘤存活率。尽管参与心磷脂合成的主要酶没有发现差异表达，但参与线粒体能量产生的蛋白质在人脑胶质瘤中的表达水平随着肿瘤分级的增加而降低。这项工作证实了人类星形细胞瘤中心磷脂的变化，并为在人类肿瘤微环境中考虑心磷脂多样性时空间感知方法提供了理论基础。心磷脂(CL)是一种线粒体脂质，在细胞呼吸、信号和细胞器膜结构中具有不同的作用。CL的含量和组成是线粒体正常功能所必需的。错乱的线粒体能量产生和信号是胶质细胞癌的关键成分，在小鼠脑胶质细胞异种移植瘤中观察到CL分子种类的改变。这项研究的目的是描述不同级别的人类星形细胞瘤的CL结构多样性趋势，并将这些趋势与异质星形细胞瘤微环境中的组织学区域相关联。为此，我们应用解吸电喷雾电离-高场非对称离子迁移率质谱仪(DESI-FAIMS-MS)对人正常皮质(N=29)、低级别星形细胞瘤(N=19)和胶质母细胞瘤(N=28)组织中CL分子种类进行了定位。利用该平台，我们从正常大脑皮层标本中检测到46种CL和12种单溶心磷脂。从胶质母细胞瘤组织中检测到的CL图谱与从正常和较低级别肿瘤中检测到的CL相比，缺乏含有CL物种的更长链多不饱和脂肪酸的多样性和丰富性。CL曲线与肿瘤存活率和肿瘤浸润性的趋势相关。通过串联MS实验对CL物种的结构进行表征，发现星形细胞瘤组织的脂肪酸和双键异构体组成与正常皮质和胶质母细胞瘤组织相比有所不同。使用GlioVis平台分析来自CGGA数据集的星形细胞瘤基因表达数据。在高级别肿瘤与低级别肿瘤中，观察到几个线粒体呼吸酶编码基因的表达降低，但心磷脂合成酶CRLS1的表达没有显著差异。
Cardiolipin is an important mitochondrial lipid for organelle and cellular energy production. Cardiolipin has been found in altered abundance and diversity in glioma xenograft models. Here, we utilize mass spectrometry imaging to map cardiolipin alterations in human normal and astrocytoma tumors in the histologically diverse tumor microenvironment. Longer chain cardiolipin species were detected at significantly lower relative abundance in tumor tissues versus normal cortex. Cardiolipin diversity correlated with histological trends in the tumor microenvironment including tumor cell invasion and tumor viability. The expression level of proteins involved in mitochondrial energy production was found to decrease with increasing tumor grade among human glioma tumors, though the major enzyme involved in cardiolipin synthesis was not found to be differentially expressed. This work provides confirmation of cardiolipin alterations in human astrocytomas and provides rationale for a spatially aware approach when considering cardiolipin diversity in the human tumor microenvironment. Cardiolipin (CL) is a mitochondrial lipid with diverse roles in cellular respiration, signaling, and organelle membrane structure. CL content and composition are essential for proper mitochondrial function. Deranged mitochondrial energy production and signaling are key components of glial cell cancers and altered CL molecular species have been observed in mouse brain glial cell xenograft tumors. The objective of this study was to describe CL structural diversity trends in human astrocytoma tumors of varying grades and correlate these trends with histological regions within the heterogeneous astrocytoma microenvironment. To this aim, we applied desorption electrospray ionization coupled with high field asymmetric ion mobility mass spectrometry (DESI-FAIMS-MS) to map CL molecular species in human normal cortex (N = 29), lower-grade astrocytoma (N = 19), and glioblastoma (N = 28) tissues. With this platform, we detected 46 CL species and 12 monolysocardiolipin species from normal cortex samples. CL profiles detected from glioblastoma tissues lacked diversity and abundance of longer chain polyunsaturated fatty acid containing CL species when compared to CL detected from normal and lower-grade tumors. CL profiles correlated with trends in tumor viability and tumor infiltration. Structural characterization of the CL species by tandem MS experiments revealed differences in fatty acid and double bond isomer composition among astrocytoma tissues compared with normal cortex and glioblastoma tissues. The GlioVis platform was used to analyze astrocytoma gene expression data from the CGGA dataset. Decreased expression of several mitochondrial respiratory enzyme encoding-genes was observed for higher-grade versus lower-grade tumors, however no significant difference was observed for cardiolipin synthesis enzyme CRLS1.
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影响因子：
7.4
作者：
Klein DR;Holden DD;Brodbelt JS
通讯作者：
Brodbelt JS
通过质谱法对组织中脂质生物化学的MALDI成像。
影响因子：
62.1
作者：
Berry, Karin A. Zemski;Hankin, Joseph A.;Barkley, Robert M.;Spraggins, Jeffrey M.;Caprioli, Richard M.;Murphy, Robert C.
通讯作者：
Murphy, Robert C.
影响因子：
1.9
作者：
Kiebish, Michael A.;Han, Xianlin;Seyfried, Thomas N.
通讯作者：
Seyfried, Thomas N.
影响因子：
5.6
作者：
Ahmadpour ST;Mahéo K;Servais S;Brisson L;Dumas JF
通讯作者：
Dumas JF
影响因子：
3.3
作者：
Howe, FA;Barton, SJ;Griffiths, JR
通讯作者：
Griffiths, JR