Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells
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Hongzhong Li1, Bing Yang1, Jing Huang1, Yong Lin1, Tingxiu Xiang1, Jingyuan Wan2, Hongyuan Li1, Salem Chouaib3, Guosheng Ren1
1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2Department of Pharmacology, Chongqing Medical University, Chongqing, China
3Unite INSERM U753, Institut de Cancerologie Gustave Roussy, Paris, France
Guosheng Ren, e-mail: firstname.lastname@example.org
Keywords: tumor microenvironment, macrophages, breast cancer, cyclooxygenase-2, prostaglandin E2
Received: May 13, 2015 Accepted: July 28, 2015 Published: August 10, 2015
Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2+ TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2+ TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy.
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