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


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 NF?B/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.

SUBMITTER: Hao J 

PROVIDER: S-EPMC5932212 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Hao Jiaqing J   Yan Fei F   Zhang Yuwen Y   Triplett Ashley A   Zhang Ying Y   Schultz Debra A DA   Sun Yanwen Y   Zeng Jun J   Silverstein Kevin A T KAT   Zheng Qi Q   Bernlohr David A DA   Cleary Margot P MP   Egilmez Nejat K NK   Sauter Edward E   Liu Shujun S   Suttles Jill J   Li Bing B  

Cancer research 20180206 9


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 a  ...[more]

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