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

doi:10.1158/0008-5472.CAN-17-2465

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

Biochemistry, Molecular Biology, and Biophysics (CBS)

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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 language	English (US)
Pages (from-to)	2343-2355
Number of pages	13
Journal	Cancer Research
Volume	78
Issue number	9
DOIs	https://doi.org/10.1158/0008-5472.CAN-17-2465
State	Published - May 1 2018

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Publisher Copyright:
© 2018 American Association for Cancer Research.

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Hao, J., Yan, F., Zhang, Y., Triplett, A., Zhang, Y., Schultz, D. A., Sun, Y., Zeng, J., Silverstein, K. A. T., Zheng, Q., Bernlohr, D. A., Cleary, M. P., Egilmez, N. K., Sauter, E., Liu, S., Suttles, J., & Li, B. (2018). Expression of adipocyte/macrophage fatty acid–binding protein in tumor-associated macrophages promotes breast cancer progression. Cancer Research, 78(9), 2343-2355. https://doi.org/10.1158/0008-5472.CAN-17-2465

Hao, J, Yan, F, Zhang, Y, Triplett, A, Zhang, Y, Schultz, DA, Sun, Y, Zeng, J, Silverstein, KAT, Zheng, Q, Bernlohr, DA, Cleary, MP, Egilmez, NK, Sauter, E, Liu, S, Suttles, J & Li, B 2018, 'Expression of adipocyte/macrophage fatty acid–binding protein in tumor-associated macrophages promotes breast cancer progression', Cancer Research, vol. 78, no. 9, pp. 2343-2355. https://doi.org/10.1158/0008-5472.CAN-17-2465

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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 {\th} F4/ 80 {\th} 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.",

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AU - Schultz, Debra A.

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AU - Zeng, Jun

AU - Silverstein, Kevin A.T.

AU - Zheng, Qi

AU - Bernlohr, David A.

AU - Cleary, Margot P.

AU - Egilmez, Nejat K.

AU - Sauter, Edward

AU - Liu, Shujun

AU - Suttles, Jill

AU - Li, Bing

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N2 - 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.

AB - 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.

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

Abstract

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