GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

被引：10

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：

日本学术振兴会; 美国国家卫生研究院; 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

共 90 条

[1] Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins
Adeyo, O.
Goulbourne, C. N.
Bensadoun, A.
Beigneux, A. P.
Fong, L. G.
Young, S. G.
[J]. JOURNAL OF INTERNAL MEDICINE, 2012, 272 (06) : 528 - 540
[2] Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions
Agnihotri, Sameer
Zadeh, Gelareh
[J]. NEURO-ONCOLOGY, 2016, 18 (02) : 160 - 172
[3] Mutating a conserved cysteine in GPIHBP1 reduces amounts of GPIHBP1 in capillaries and abolishes LPL binding
Allan, Christopher M.
Jung, Cris J.
Larsson, Mikael
Heizer, Patrick J.
Tu, Yiping
Sandoval, Norma P.
Dang, Tiffany Ly P.
Jung, Rachel S.
Beigneux, Anne P.
de Jong, Pieter J.
Fong, Loren G.
Young, Stephen G.
[J]. JOURNAL OF LIPID RESEARCH, 2017, 58 (07) : 1453 - 1461
[4] Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries
Allan, Christopher M.
Larsson, Mikael
Jung, Rachel S.
Ploug, Michael
Bensadoun, Andre
Beigneux, Anne P.
Fong, Loren G.
Young, Stephen G.
[J]. JOURNAL OF LIPID RESEARCH, 2017, 58 (01) : 216 - 225
[5] An LPL-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to GPIHBP1
Allan, Christopher M.
Larsson, Mikael
Hu, Xuchen
He, Cuiwen
Jung, Rachel S.
Mapar, Alaleh
Voss, Constance
Miyashita, Kazuya
Machida, Tetsuo
Murakami, Masami
Nakajima, Katsuyuki
Bensadoun, Andre
Ploug, Michael
Fong, Loren G.
Young, Stephen G.
Beigneux, Anne P.
[J]. JOURNAL OF LIPID RESEARCH, 2016, 57 (10) : 1889 - 1898
[6] Multiplexed ion beam imaging of human breast tumors
Angelo, Michael
Bendall, Sean C.
Finck, Rachel
Hale, Matthew B.
Hitzman, Chuck
Borowsky, Alexander D.
Levenson, Richard M.
Lowe, John B.
Liu, Scot D.
Zhao, Shuchun
Natkunam, Yasodha
Nolan, Garry P.
[J]. NATURE MEDICINE, 2014, 20 (04) : 436 - +
[7] Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons
Beigneux, Anne P.
Davies, Brandon S. J.
Gin, Peter
Weinstein, Michael M.
Farber, Emily
Qiao, Xin
Peale, Franklin
Bunting, Stuart
Walzem, Rosemary L.
Wong, Jinny S.
Blaner, William S.
Ding, Zhi-Ming
Melford, Kristan
Wongsiriroj, Nuttaporn
Shu, Xiao
de Sauvage, Fred
Ryan, Robert O.
Fong, Loren G.
Bensadoun, Andre
Young, Stephen G.
[J]. CELL METABOLISM, 2007, 5 (04) : 279 - 291
[8] Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase
Beigneux, Anne P.
Gin, Peter
Davies, Brandon S. J.
Weinstein, Michael M.
Bensadoun, Andre
Fong, Loren G.
Young, Stephen G.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (44) : 30240 - 30247
[9] BENZEEV O, 1990, J LIPID RES, V31, P1307
[10] BESSESEN DH, 1993, J LIPID RES, V34, P229

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