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Int J Biol Sci 2016; 12(12):1533-1543. doi:10.7150/ijbs.15943

Research Paper

Cyclooxygenase-2 in tumor-associated macrophages promotes metastatic potential of breast cancer cells through Akt pathway

Lu Gan1,2, Zhu Qiu1, Jing Huang1, Yunhai Li1,3, Hongyan Huang1, Tingxiu Xiang1, Jingyuan Wan4, Tianli Hui1, Yong Lin1, Hongzhong Li1,3✉, Guosheng Ren1,3✉

1. Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;
2. Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;
3. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;
4. Department of Pharmacology, Chongqing Medical University, Chongqing, China.

Abstract

Tumor-associated macrophages (TAMs) promote cancer development and progression by releasing various cytokines and chemokines. Previously, we have found that the number of COX-2+ TAMs was associated with lymph node metastasis in breast cancer. However, the mechanism remains enigmatic. In this study, we show that COX-2 in breast TAMs enhances the metastatic potential of breast cancer cells. COX-2 in TAMs induces MMP-9 expression and promotes epithelial-mesenchymal transition (EMT) in breast cancer cells. In addition, COX-2/PGE2 induces IL-6 release in macrophages. Furthermore, we find that the activation of Akt pathway in cancer cells is crucial for the pro-metastatic effect of COX-2+ TAMs by regulating MMP-9 and EMT. These findings indicate that TAMs facilitate breast cancer cell metastasis through COX-2-mediated intercellular communication.

Keywords: Tumor microenvironment, macrophages, breast cancer, cyclooxygenase-2.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Gan L, Qiu Z, Huang J, Li Y, Huang H, Xiang T, Wan J, Hui T, Lin Y, Li H, Ren G. Cyclooxygenase-2 in tumor-associated macrophages promotes metastatic potential of breast cancer cells through Akt pathway. Int J Biol Sci 2016; 12(12):1533-1543. doi:10.7150/ijbs.15943. Available from http://www.ijbs.com/v12p1533.htm