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

Cristiana Tanase,Mihail Eugen Hinescu,Sevinci Pop,Ancuța-Augustina Gheorghișan-Gălățeanu,Maria Dudau,Simona Mihai,Elena Codrici,Ionela Daniela Popescu,Ana Maria Dobri,Ana Maria Enciu

doi:10.3390/ijms23020604

Abstract

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.

Highlights

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor genetic heterogeneity [1,2,3] and extensive epigenetic mechanism dysregulations [4,5]
Noting the fact that cancer stem cells have a high expression of CD36 and increased polyunsaturated fatty acid levels [71], this scavenger receptor could be related to a self-renewal and survival mechanism of glioma cells
Thrombospondins (TSP-1–TSP-5) are proteins found in the extracellular matrix (ECM), with multiple effects mediated by interaction with various cell receptors, and with cytokines, growth factors, proteases, and other stromal cell proteins [83,84]

Summary

Introduction

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor genetic heterogeneity [1,2,3] and extensive epigenetic mechanism dysregulations [4,5]. Noting the fact that cancer stem cells have a high expression of CD36 and increased polyunsaturated fatty acid levels [71], this scavenger receptor could be related to a self-renewal and survival mechanism of glioma cells. Higher levels of this protein are linked with poor prognosis in both glioma and GBM tumors [68]. CD36 is a critical receptor for regulating lipid metabolism in tumor microenvironment cells and promoting tumor growth and metastasis; CD36 may become a potential biomarker for clinical diagnosis/prognosis as well as a target for cancer therapy

Thrombospondin-1

CD36 and Thrombospondin-1 in Glioblastoma

CD47 and Thrombospondin-1 in Glioblastoma

Findings

Conclusions