期刊
ONCOTARGET
卷 6, 期 30, 页码 29637-29650出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4936
关键词
tumor microenvironment; macrophages; breast cancer; cyclooxygenase-2; prostaglandin E-2
资金
- National Natural Science Foundation of China [81102007, 81472475]
- International S&T Cooperation Program of China (ISTCP) [2012DFA10650]
- National High Technology Research and Development Program of China (863 Program) [2012AA020101]
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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