Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages

Cancer Res. 2014 Jun 1;74(11):2986-98. doi: 10.1158/0008-5472.CAN-13-2689. Epub 2014 Apr 8.

Abstract

Fatty acid-binding proteins (FABP) are known central regulators of both metabolic and inflammatory pathways, but their role in tumor development remains largely unexplored. Here, we report that host expression of epidermal FABP (E-FABP) protects against mammary tumor growth. We find that E-FABP is highly expressed in macrophages, particularly in a specific subset, promoting their antitumor activity. In the tumor stroma, E-FABP-expressing tumor-associated macrophages (TAM) produce high levels of IFN-β through upregulation of lipid droplet formation in response to tumors. E-FABP-mediated IFN-β signaling can further enhance recruitment of tumoricidal effector cells, in particular natural killer cells, to the tumor stroma for antitumor activity. These findings identify E-FABP as a new protective factor to strengthen IFN-β responses against tumor growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epidermis / metabolism
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / immunology
  • Fatty Acid-Binding Proteins / metabolism*
  • Female
  • Gene Expression / genetics
  • Humans
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • Interferon-beta / metabolism*
  • Killer Cells, Natural / metabolism
  • Lipids / genetics
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Tumor Cells, Cultured

Substances

  • Fatty Acid-Binding Proteins
  • Lipids
  • Interferon-beta