期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 12, 期 12, 页码 1533-1543出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.15943
关键词
Tumor microenvironment; macrophages; breast cancer; cyclooxygenase-2
资金
- National Natural Science Foundation of China [81472475, 81102007]
- Health and Family Planning Commission of Chongqing [2011-2-008]
- Scientific Research Foundation of Chongqing Medical University [201408]
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/PGE(2) 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.
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