The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity

Nat Commun. 2015 Feb 27;6:6354. doi: 10.1038/ncomms7354.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Carcinoma / immunology*
  • Carcinoma / physiopathology
  • Cell Line, Tumor
  • Cholesterol / metabolism*
  • Flow Cytometry
  • Fluorescence
  • Homeostasis / physiology*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Melanoma / immunology*
  • Melanoma / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / physiopathology

Substances

  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Lipoproteins
  • Cholesterol