Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

Automated summary

Glioblastoma (GBM) is an aggressive tumor with high heterogeneity. The accumulation of fatty acid metabolites is associated with low survival rates in patients with high-grade gliomas. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), and the involvement of FA transport proteins and FA translocases are crucial for PUFAs transportation through the blood-brain barrier and delivery to brain cells. Among them, the CD36 FA translocase plays a role in the uptake of long-chain FAs and oxidized lipoproteins. Furthermore, the interaction between CD36 and thrombospondin-1 (TSP-1) has an important role in glioma cell invasion and angiogenesis in GBM. The interconnection and interrelationship between FA, CD36, CD47, and their ligand TSP-1 have been highlighted in recent research to exert a cumulative effect on the modulation of the GBM molecular network.