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Cancer Stem Cell‐Specific Scavenger Receptor CD36 Drives Glioblastoma Progression
Author(s) -
Hale James S.,
Otvos Balint,
Sinyuk Maksim,
Alvarado Alvaro G.,
Hitomi Masahiro,
Stoltz Kevin,
Wu Qiulian,
Flavahan William,
Levison Bruce,
Johansen Mette L.,
Schmitt David,
Neltner Janna M.,
Huang Ping,
Ren Bin,
Sloan Andrew E.,
Silverstein Roy L.,
Gladson Candece L.,
DiDonato Joseph A.,
Brown J. Mark,
McIntyre Thomas,
Hazen Stanley L.,
Horbinski Craig,
Rich Jeremy N.,
Lathia Justin D.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1716
Subject(s) - scavenger receptor , cd36 , cancer stem cell , biology , cancer research , stem cell , tumor microenvironment , population , cancer cell , microbiology and biotechnology , cancer , receptor , immunology , immune system , lipoprotein , cholesterol , medicine , endocrinology , biochemistry , genetics , environmental health
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. S tem C ells 2014;32:1746–1758

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