Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells.
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.
['Li|Hongzhong|H|', 'Yang|Bing|B|', 'Huang|Jing|J|', 'Lin|Yong|Y|', 'Xiang|Tingxiu|T|', 'Wan|Jingyuan|J|', 'Li|Hongyuan|H|', 'Chouaib|Salem|S|', 'Ren|Guosheng|G|']
D000818:Animals D000970:Antineoplastic Agents D051017:Apoptosis Regulatory Proteins D015153:Blotting, Western D001943:Breast Neoplasms D002460:Cell Line D045744:Cell Line, Tumor D002470:Cell Survival D002478:Cells, Cultured D018920:Coculture Techniques D051546:Cyclooxygenase 2 D025461:Feedback, Physiological D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D061986:MCF-7 Cells D008264:Macrophages D008812:Mice, Hairless D018345:Mice, Knockout D016513:Mice, SCID D008875:Middle Aged D019869:Phosphatidylinositol 3-Kinases D011379:Prognosis D020133:Reverse Transcriptase Polymerase Chain Reaction D015398:Signal Transduction
cyclooxygenase-2 macrophages breast cancer prostaglandin E2 tumor microenvironment