The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.
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.
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Duygu
D
Sag
Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
Caglar
C
Cekic
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Runpei
R
Wu
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Joel
J
Linden
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Catherine C
CC
Hedrick
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002277:Carcinoma / Q000276:immunology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D005434:Flow Cytometry; D005453:Fluorescence; D006706:Homeostasis / Q000502:physiology*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000503:physiopathology
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D002784:Cholesterol