GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

被引：11

作者：

Hu, Xuchen ^{[1
]}

Matsumoto, Ken ^{[2
]}

Jung, Rachel S. ^{[1
]}

Weston, Thomas A. ^{[1
]}

Heizer, Patrick J. ^{[1
]}

He, Cuiwen ^{[1
]}

Sandoval, Norma P. ^{[1
]}

Allan, Christopher M. ^{[1
]}

Tu, Yiping ^{[1
]}

Vinters, Harry V. ^{[3
]}

Liau, Linda M. ^{[4
,5
]}

Ellison, Rochelle M. ^{[1
]}

Morales, Jazmin E. ^{[1
]}

Baufeld, Lynn J. ^{[6
,7
]}

Bayley, Nicholas A. ^{[6
,7
]}

He, Liqun ^{[8
]}

Betsholtz, Christer ^{[8
,9
]}

Beigneux, Anne P., I ^{[1
]}

Nathanson, David A. ^{[6
,7
]}

Gerhardt, Holger ^{[2
,10
]}

Young, Stephen G. ^{[1
,11
]}

Fong, Loren G. ^{[1
]}

Jian, Haibo ^{[1
,12
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[2] VIB KU Leuven Ctr Canc Biol CCB, Leuven, Belgium

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, JCCC, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Ahmanson Translat Imaging Div, Los Angeles, CA 90095 USA

[8] Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[9] Karolinska Inst, ICMC, Huddinge, Sweden

[10] Max Delbruck Ctr Mol Med, Berlin, Germany

[11] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[12] Univ Western Australia, Sch Mol Sci, Perth, WA, Australia

来源：

ELIFE | 2019年 / 8卷

基金：

美国国家卫生研究院; 日本学术振兴会; 澳大利亚研究理事会;

关键词：

BLOOD-BRAIN-BARRIER; ENDOTHELIAL GROWTH-FACTOR; LIPASE MESSENGER-RNA; FATTY-ACID OXIDATION; GLUCOSE-METABOLISM; HUMAN GLIOBLASTOMA; BINDING PROTEIN-1; CELLS; RAT; PATHWAYS;

D O I：

10.7554/eLife.47178

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. 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 the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show 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.

引用

页数：29

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