A mass spectrometry imaging and lipidomic investigation reveals aberrant lipid metabolism in the orthotopic mouse glioma

被引:11
|
作者
Wang, Hay-Yan J. [1 ]
Huang, Chiung-Yin [2 ,3 ]
Wei, Kuo-Chen [2 ,3 ,4 ,5 ]
Hung, Kuo-Chen [6 ]
机构
[1] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung, Taiwan
[2] Chang Gung Mem Hosp, Neurosci Res Ctr, Taoyuan, Taiwan
[3] New Taipei Municipal TuCheng Hosp, Dept Neurosurg, New Taipei, Taiwan
[4] Chang Gung Mem Hosp, Dept Neurosurg, Taoyuan, Taiwan
[5] Chang Gung Univ, Sch Med, Taoyuan, Taiwan
[6] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Dept Surg, Coll Med, Kaohsiung, Taiwan
关键词
tumor pathology; phospholipids; sphingolipids; MALDI MS imaging; unsupervised clustering; RAT-BRAIN SECTIONS; FATTY-ACID; CANCER; GLIOBLASTOMA; TRANSFORMATION; PHOSPHOLIPIDS; TUMORS; BOVINE; ROLES;
D O I
10.1016/j.jlr.2022.100304
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lipids perform multiple biological functions and reflect the physiology and pathology of cells, tissues, and organs. Here, we sought to understand lipid content in relation to tumor pathology by characterizing phospholipids and sphingolipids in the orthotopic mouse glioma using MALDI MS imaging (MSI) and LC-MS/MS. Unsupervised clustering analysis of the MALDI-MSI data segmented the coronal tumoral brain section into 10 histopathologically salient regions. Heterogeneous decrease of the common saturated phosphatidyl-cholines (PCs) in the tumor was accompanied by the increase of analogous PCs with one or two additional fatty acyl double bonds and increased lysoPCs. Polyunsaturated fatty acyl-PCs and ether PCs highlighted the striatal tumor margins, whereas the distributions of other PCs differentiated the cortical and striatal tumor parenchyma. We detected a reduction of SM d18:1/18: 0 and the heterogeneous mild increase of SM d18:1/16:0 in the tumor, whereas ceramides accumulated only in a small patch deep in the tumoral parenchyma. LC- MS/MS analyses of phospholipids and sphingolipids complemented the MALDI-MSI observation, providing a snapshot of these lipids in the tumor. Finally, the proposed mechanisms responsible for the tumoral lipid changes were contrasted with our interrogation of gene expression in human glioma. Together, these lipidomic results unveil the aberrant and heterogeneous lipid metabolism in mouse glioma where multiple lipid-associated signaling pathways underline the tumor features, promote the survival, growth, proliferation, and invasion of different tumor cell populations, and implicate the management strategy of a multiple-target approach for glioma and related brain malignancies.
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页数:14
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