The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Duygu Sag; Caglar Cekic; Runpei Wu; Joel Linden; Catherine C. Hedrick

doi:10.1038/ncomms7354

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Duygu Sag, Caglar Cekic, Runpei Wu, Joel Linden, Catherine C. Hedrick

Research output: Contribution to journal › Article › peer-review

146 Scopus citations

Abstract

ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1^-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1^-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1^-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

Original language	English (US)
Article number	6354
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7354
State	Published - Feb 27 2015
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms7354

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title = "The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity",

abstract = "ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.",

author = "Duygu Sag and Caglar Cekic and Runpei Wu and Joel Linden and Hedrick, {Catherine C.}",

note = "Funding Information: We thank Amy Blatchley, Debbi Yoakum, Fernando Vazquez, Dr Iftach Shaked, the Department of Laboratory Animal Care and the Flow Cytometry Facility at the La Jolla Institute for Allergy and Immunology (LJI) for excellent technical assistance. We thank Dr Gerhard Wingender and Dr Klaus Ley at LJI for valuable scientific contributions. We also thank Jennifer Pattison and Dr Joseph Witztum at University of California San Diego for assistance with plasma lipoprotein analysis. This work was supported by NIH R01 HL097368 (to C.C.H.) and NIH P01 HL55798 (to C.C.H.). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

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AU - Cekic, Caglar

AU - Wu, Runpei

AU - Linden, Joel

AU - Hedrick, Catherine C.

N1 - Funding Information: We thank Amy Blatchley, Debbi Yoakum, Fernando Vazquez, Dr Iftach Shaked, the Department of Laboratory Animal Care and the Flow Cytometry Facility at the La Jolla Institute for Allergy and Immunology (LJI) for excellent technical assistance. We thank Dr Gerhard Wingender and Dr Klaus Ley at LJI for valuable scientific contributions. We also thank Jennifer Pattison and Dr Joseph Witztum at University of California San Diego for assistance with plasma lipoprotein analysis. This work was supported by NIH R01 HL097368 (to C.C.H.) and NIH P01 HL55798 (to C.C.H.). Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/2/27

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N2 - ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1-/- mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1-/- mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1-/- macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

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The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Abstract

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