Expression of adipocyte/macrophage fatty acid–binding protein in tumor-associated macrophages promotes breast cancer progression

Jiaqing Hao, Fei Yan, Yuwen Zhang, Ashley Triplett, Ying Zhang, Debra A. Schultz, Yanwen Sun, Jun Zeng, Kevin A.T. Silverstein, Qi Zheng, David A. Bernlohr, Margot P. Cleary, Nejat K. Egilmez, Edward Sauter, Shujun Liu, Jill Suttles, Bing Li

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 þ F4/ 80 þ MHCIILy6C phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFkB/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.

5. 2018 AACR.

Original languageEnglish (US)
Pages (from-to)2343-2355
Number of pages13
JournalCancer Research
Volume78
Issue number9
DOIs
StatePublished - May 1 2018

Bibliographical note

Funding Information:
The authors thank the Mayo Clinic Genome Analysis Core for the help with performing microRNA expression array of macrophages and Minnesota Supercomputing Institute for computing resources used for the microarray analysis. This work was supported by NIH R01 grants CA18098601A1 (to B. Li), CA17767901A1 (to B. Li), and AI048850 (to J. Suttles).

Publisher Copyright:
© 2018 American Association for Cancer Research.

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