GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

Abstract
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Abstract

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. The GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1–LPL complex is crucial for generating lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent in capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We document, by NanoSIMS imaging, that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.

Data availability

All data generated during this study are included in the manuscript and supporting files.

The following previously published data sets were used

1. He L
2. Vanlandewijck M
3. Mae MA
4. Andrae J
5. Ando K
6. Del Gaudio F
(2018) Data Descriptor | OPEN | Published: 21 August 2018 Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types
Vascular Single Cell.

http://betsholtzlab.org/VascularSingleCells/database.html

Article and author information

Author details

Xuchen Hu

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Ken Matsumoto

Vascular Patterning Lab, VIB-KU Leuven Center for Cancer Biology (CCB), Leuven, Belgium

Competing interests
No competing interests declared.
Rachel S Jung

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Thomas A Weston

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Patrick J Heizer

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Cuiwen He

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Norma P Sandoval

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Christopher M Allan

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Yiping Tu

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Harry V Vinters

Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Linda M Liau

Department of Neurosurgery, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Rochelle M Ellison

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Jazmin E Morales

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Lynn J Baufeld

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Nicholas A Bayley

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Liqun He

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Competing interests
No competing interests declared.
Christer Betsholtz

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

Competing interests
No competing interests declared.
Anne P Beigneux

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
David A Nathanson

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

Competing interests
No competing interests declared.
Holger Gerhardt

Integrative Vascular Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Competing interests
Holger Gerhardt, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0002-3030-0384
Stephen G Young

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
sgyoung@mednet.ucla.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7270-3176
Loren G Fong

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
lfong@mednet.ucla.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4465-5290
Haibo Jiang

Department of Medicine, University of California, Los Angeles, Los Angeles, United States

For correspondence
haibo.jiang@uwa.edu.au

Competing interests
No competing interests declared.

Funding

National Heart, Lung, and Blood Institute (HL090553)

Stephen G Young

National Heart, Lung, and Blood Institute (HL087228)

Stephen G Young

National Heart, Lung, and Blood Institute (HL125335)

Stephen G Young

Foundation Leduq (12CVD04)

Stephen G Young

Ruth L. Kirschstein National Research Service Award (T32HL69766)

Xuchen Hu

National Institute of General Medical Sciences (GM008042)

Xuchen Hu

NCI Brain Tumor SPORE (P50-CA211015)

Linda M Liau

Stichting Tegen Kanker (2012‐181)

Holger Gerhardt

Stichting Tegen Kanker (2018-074)

Holger Gerhardt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal housing and experimental protocols were approved by UCLA's Animal Research Committee (ARC; 2004-125-51, 2016-005) and the Institutional Animal Care and Research Advisory Committee of the KU Leuven (085/2016). The animals were housed in an AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care International)-approved facility and cared for according to guidelines established by UCLA's Animal Research Committee.

Human subjects: All tissue samples from patients were obtained after informed consent and with approval from the UCLA Institutional Review Board (IRB; protocol 10-000655).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.