The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Date
2015
Authors
Sag, D.
Cekic, C.
Wu, R.
Linden J.
Hedrick, C.C.
Advisor
Instructor
Source Title
Nature Communications
Print ISSN
20411723
Electronic ISSN
Publisher
Nature Publishing Group
Volume
6
Issue
Pages
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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. © 2015 Macmillan Publishers Limited. All rights reserved.

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Keywords
ABC transporter G1, immunoglobulin enhancer binding protein, cancer, cell organelle, homeostasis, immunity, inhibition, organic compound, phenotype, tumor, animal cell, animal experiment, apoptosis, Article, bladder carcinoma, bone marrow cell, cholesterol homeostasis, cholesterol transport, cytotoxicity, homeostasis, in vitro study, macrophage function, melanoma B16, mouse, nonhuman, tumor cell, tumor growth, tumor immunity, Mus
Citation
Published Version (Please cite this version)