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
phosphatidylcholines (PCs) in the
tumor was accompanied by the increase of analogous PCs with one or two additional fatty acyl double bonds and increased lyso-PCs. 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.