期刊
STEM CELLS
卷 32, 期 7, 页码 1746-1758出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.1716
关键词
Cancer stem cells; Glioma; Stem cell-microenvironment interactions; Self-renewal
资金
- NIH [CA157948]
- National Institutes of Health [NS083629, CA112958, CA154130, CA169117, K08 CA155764, RR020171, P01 HL076491, CA152883, CA175120, CA137443, NS063971, CA128269, CA101954, CA116257]
- Lerner Research Institute
- Voices Against Brain Cancer
- Ohio Cancer Research Associates
- V Foundation for Cancer Research
- American Cancer Society [IRG-91-022-18]
- Cleveland Clinic Product Development Fund
- University of Kentucky College of Medicine Physician Scientist Program
- Cancer Genome Atlas (TCGA) Project
- Ben & Catherine Ivy Foundation
- Kimble Foundation
- Peter B. Cristal Endowment
- Ohio Department of Development Technology [09-071]
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.
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