Mass spectrometry imaging discriminates glioblastoma tumor cell subpopulations and different microvascular formations based on their lipid profiles.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 10 2022
12 10 2022
Historique:
received:
24
03
2022
accepted:
10
10
2022
entrez:
12
10
2022
pubmed:
13
10
2022
medline:
15
10
2022
Statut:
epublish
Résumé
Glioblastoma is a prevalent malignant brain tumor and despite clinical intervention, tumor recurrence is frequent and usually fatal. Genomic investigations have provided a greater understanding of molecular heterogeneity in glioblastoma, yet there are still no curative treatments, and the prognosis has remained unchanged. The aggressive nature of glioblastoma is attributed to the heterogeneity in tumor cell subpopulations and aberrant microvascular proliferation. Ganglioside-directed immunotherapy and membrane lipid therapy have shown efficacy in the treatment of glioblastoma. To truly harness these novel therapeutics and develop a regimen that improves clinical outcome, a greater understanding of the altered lipidomic profiles within the glioblastoma tumor microenvironment is urgently needed. In this work, high resolution mass spectrometry imaging was utilized to investigate lipid heterogeneity in human glioblastoma samples. Data presented offers the first insight into the histology-specific accumulation of lipids involved in cell metabolism and signaling. Cardiolipins, phosphatidylinositol, ceramide-1-phosphate, and gangliosides, including the glioblastoma stem cell marker, GD3, were shown to differentially accumulate in tumor and endothelial cell subpopulations. Conversely, a reduction in sphingomyelins and sulfatides were detected in tumor cell regions. Cellular accumulation for each lipid class was dependent upon their fatty acid residue composition, highlighting the importance of understanding lipid structure-function relationships. Discriminating ions were identified and correlated to histopathology and Ki67 proliferation index. These results identified multiple lipids within the glioblastoma microenvironment that warrant further investigation for the development of predictive biomarkers and lipid-based therapeutics.
Identifiants
pubmed: 36224354
doi: 10.1038/s41598-022-22093-4
pii: 10.1038/s41598-022-22093-4
pmc: PMC9556690
doi:
Substances chimiques
Cardiolipins
0
Ceramides
0
Fatty Acids
0
Gangliosides
0
Ki-67 Antigen
0
Phosphates
0
Phosphatidylinositols
0
Sphingomyelins
0
Sulfoglycosphingolipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17069Informations de copyright
© 2022. The Author(s).
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