PMID- 25724068 OWN - NLM STAT- MEDLINE DCOM- 20160208 LR - 20181202 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 6 DP - 2015 Feb 27 TI - The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity. PG - 6354 LID - 10.1038/ncomms7354 [doi] AB - 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-kappaB 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. FAU - Sag, Duygu AU - Sag D AD - Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. FAU - Cekic, Caglar AU - Cekic C AD - Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey. FAU - Wu, Runpei AU - Wu R AD - Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. FAU - Linden, Joel AU - Linden J AD - Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. FAU - Hedrick, Catherine C AU - Hedrick CC AD - Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA. LA - eng GR - P01 HL055798/HL/NHLBI NIH HHS/United States GR - R01 HL097368/HL/NHLBI NIH HHS/United States GR - S10 RR027366/RR/NCRR NIH HHS/United States GR - P01 HL55798/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150227 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Lipoproteins) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/*metabolism MH - Animals MH - Carcinoma/*immunology/physiopathology MH - Cell Line, Tumor MH - Cholesterol/*metabolism MH - Flow Cytometry MH - Fluorescence MH - Homeostasis/*physiology MH - Lipoproteins/genetics/*metabolism MH - Macrophages/cytology/*immunology MH - Melanoma/*immunology/physiopathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Real-Time Polymerase Chain Reaction MH - Urinary Bladder Neoplasms/*immunology/physiopathology PMC - PMC4347884 MID - NIHMS658095 EDAT- 2015/02/28 06:00 MHDA- 2016/02/09 06:00 PMCR- 2015/08/27 CRDT- 2015/02/28 06:00 PHST- 2014/04/21 00:00 [received] PHST- 2015/01/22 00:00 [accepted] PHST- 2015/02/28 06:00 [entrez] PHST- 2015/02/28 06:00 [pubmed] PHST- 2016/02/09 06:00 [medline] PHST- 2015/08/27 00:00 [pmc-release] AID - ncomms7354 [pii] AID - 10.1038/ncomms7354 [doi] PST - epublish SO - Nat Commun. 2015 Feb 27;6:6354. doi: 10.1038/ncomms7354.