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New paper published describes how proteoglycan-dependent endocytosis feeds glioma's lipid uptake

Schematic drawing of the association between uptake, HSPG and LD loaded phenotype.

On this new paper released on March 2021, Myriam Cerezo-Magaña and collaborators explore the interplay between hypoxia, lipid scavenging, proteoglycans and lipid storage. The paper, titled "Hypoxic Induction of Exosome Uptake through Proteoglycan-Dependent Endocytosis Fuels the Lipid Droplet Phenotype in Glioma" and published at Molecular Cancer Research, shows that exosome-like extracellular vesicles (EVs) may serve anabolic functions by transforming hypoxic, patient-derived human glioblastoma cell lines into a lipid loaded phenotype.

In this study, evidence shows that EVs can fuel hypoxic glioma cells to acquire a lipid droplet (LD+) phenotype and such effect is associated with increased EV internalization through a hypoxia-sensitive mechanism dependent on heparan sulfate proteoglycan (HSPG) receptor and lipid raft–mediated endocytosis. The authors found that the hypoxia-mediated HSPG-dependent EV uptake could be further evidenced by the reversal of EV-mediated lipid droplet loading by targeting of HSPG receptor function.

This research sheds light into the mechanistics of glioma adaptation in the hypoxic tumor microenvironment and motivates further studies aimed at establishing therapeutic strategies targeted at the endocytic machinery that should be combined with available inhibitors of lipid biosynthesis.