Version 1
: Received: 21 September 2023 / Approved: 21 September 2023 / Online: 21 September 2023 (13:04:57 CEST)
How to cite:
Maraqah, H.; Aboubechara, J. P.; Abu-Asab, M.; Lee, H. S.; Aboud, O. Excessive Lipid Production Shapes Glioma Tumor Microenvironment. Preprints2023, 2023091490. https://doi.org/10.20944/preprints202309.1490.v1
Maraqah, H.; Aboubechara, J. P.; Abu-Asab, M.; Lee, H. S.; Aboud, O. Excessive Lipid Production Shapes Glioma Tumor Microenvironment. Preprints 2023, 2023091490. https://doi.org/10.20944/preprints202309.1490.v1
Maraqah, H.; Aboubechara, J. P.; Abu-Asab, M.; Lee, H. S.; Aboud, O. Excessive Lipid Production Shapes Glioma Tumor Microenvironment. Preprints2023, 2023091490. https://doi.org/10.20944/preprints202309.1490.v1
APA Style
Maraqah, H., Aboubechara, J. P., Abu-Asab, M., Lee, H. S., & Aboud, O. (2023). Excessive Lipid Production Shapes Glioma Tumor Microenvironment. Preprints. https://doi.org/10.20944/preprints202309.1490.v1
Chicago/Turabian Style
Maraqah, H., Han Sung Lee and Orwa Aboud. 2023 "Excessive Lipid Production Shapes Glioma Tumor Microenvironment" Preprints. https://doi.org/10.20944/preprints202309.1490.v1
Abstract
Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma (n=18) and IDH1 mutant (IDH1-mt) astrocytoma (n=12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical mem-braneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vascula-ture are shown to have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Overproduction of lipids by the tumor is suspected to be due to a combination of two processes: i) dysfunctional oxidative phosphorylation in mitochondria that causes metabolic backup and ac-cumulation of acetyl-CoA, as well as ii) the overproduction of pyruvate due to the tumor cell reli-ance on overactive glycolysis. Tumor cells use lipids for structural components but cannot use them for energy if their oxidative phosphorylation is dysfunctional, which seems to be the case in the tumor cells we examined. This lipid-rich environment, however, offers tumor cells certain advantages: protection from the immune system, non-lipophilic drugs, and oxidative stress. Our research highlights the significant presence of lipid overproduction in both IDH1-wild type glio-blastoma and IDH1-mutant astrocytoma tumors, leading to diverse lipid accumulations in var-ious cellular compartments and structures. This lipid excess stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune re-sponses, non-lipophilic drugs, and free radicals.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
