Expression of Adipocyte/Macrophage Fatty Acid-Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression

Cancer Res. 2018 May 1;78(9):2343-2355. doi: 10.1158/0008-5472.CAN-17-2465. Epub 2018 Feb 6.

Abstract

Tumor-associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically relevant markers for protumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid-binding protein (A-FABP) in TAM promotes breast cancer progression. Although upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis. Furthermore, the protumor effect of A-FABP was mediated by TAM, in particular, in a subset of TAM with a CD11b+F4/80+MHCII-Ly6C- phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFκB/miR-29b pathway. Collectively, our results suggest A-FABP as a new functional marker for protumor TAM.Significance: These findings identify A-FABP as a functional marker for protumor macrophages, thus offering a new target for tumor immunotherapy. Cancer Res; 78(9); 2343-55. ©2018 AACR.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Fatty Acid-Binding Proteins / genetics*
  • Fatty Acid-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Metastasis

Substances

  • Biomarkers, Tumor
  • Cytokines
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • MIRN29a microRNA, human
  • MicroRNAs
  • NF-kappa B