Haitham H Maraqah, John Paul Aboubechara, Mones S Abu-Asab, Han Sung Lee, Orwa Aboud
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Excessive lipid production shapes glioma tumor microenvironment.
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 membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature 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. Lipid excess in gliomas 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 responses, non-lipophilic drugs, and free radicals.
期刊介绍:
Ultrastructural Pathology is the official journal of the Society for Ultrastructural Pathology. Published bimonthly, we are the only journal to be devoted entirely to diagnostic ultrastructural pathology.
Ultrastructural Pathology is the ideal journal to publish high-quality research on the following topics:
Advances in the uses of electron microscopic and immunohistochemical techniques
Correlations of ultrastructural data with light microscopy, histochemistry, immunohistochemistry, biochemistry, cell and tissue culturing, and electron probe analysis
Important new, investigative, clinical, and diagnostic EM methods.