Faculty Collaboration Database

Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression. Stem Cells 2014 Jul;32(7):1746-58

Date

04/17/2014

Pubmed ID

24737733

Pubmed Central ID

PMC4063873

DOI

10.1002/stem.1716

Scopus ID

2-s2.0-84902578963 (requires institutional sign-in at Scopus site)   170 Citations

Abstract

Glioblastoma (GBM) contains a self-renewing, tumorigenic cancer stem cell (CSC) population which contributes to tumor propagation and therapeutic resistance. While the tumor microenvironment is essential to CSC self-renewal, the mechanisms by which CSCs sense and respond to microenvironmental conditions are poorly understood. Scavenger receptors are a broad class of membrane receptors well characterized on immune cells and instrumental in sensing apoptotic cellular debris and modified lipids. Here, we provide evidence that CSCs selectively use the scavenger receptor CD36 to promote their maintenance using patient-derived CSCs and in vivo xenograft models. CD36 expression was observed in GBM cells in addition to previously described cell types including endothelial cells, macrophages, and microglia. CD36 was enriched in CSCs and was able to functionally distinguish self-renewing cells. CD36 was coexpressed with integrin alpha 6 and CD133, previously described CSC markers, and CD36 reduction resulted in concomitant loss of integrin alpha 6 expression, self-renewal, and tumor initiation capacity. We confirmed oxidized phospholipids, ligands of CD36, were present in GBM and found that the proliferation of CSCs, but not non-CSCs, increased with exposure to oxidized low-density lipoprotein. CD36 was an informative biomarker of malignancy and negatively correlated to patient prognosis. These results provide a paradigm for CSCs to thrive by the selective enhanced expression of scavenger receptors, providing survival, and metabolic advantages.

Author List

Hale JS, Otvos B, Sinyuk M, Alvarado AG, Hitomi M, Stoltz K, Wu Q, Flavahan W, Levison B, Johansen ML, Schmitt D, Neltner JM, Huang P, Ren B, Sloan AE, Silverstein RL, Gladson CL, DiDonato JA, Brown JM, McIntyre T, Hazen SL, Horbinski C, Rich JN, Lathia JD

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain Neoplasms
CD36 Antigens
Cell Proliferation
Disease Progression
Female
Gene Expression
Glioblastoma
Kaplan-Meier Estimate
Lipoproteins, LDL
Mice, Nude
Neoplasm Transplantation
Neoplastic Stem Cells
Tumor Cells, Cultured