CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis
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Ran Liu1,*, Huiting Wei2,*, Peng Gao3, Hu Yu4, Ke Wang4, Zheng Fu2, Baohui Ju5, Meng Zhao4, Shangwen Dong6, Zhijun Li6, Yifeng He7, Yuting Huang4 and Zhi Yao2
1Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China
2Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300071, China
3University of the District of Columbia, Washington D.C., 20008, United States
4Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300040, China
5Second Hospital of Tianjin Medical University, Tianjin, 300211, China
6Tianjin Medical University General Hospital, Tianjin, 300052, China
7Department of Gynecology and Obstetrics, Renji Hospital, Shanghai, 200127, China
*These authors have contributed equally to this work
Zhi Yao, email: [email protected]
Yuting Huang, email: [email protected]
Keywords: ovarian cancer, CD47, macrophage, phagocytosis, monoclonal antibody
Received: January 20, 2017 Accepted: February 22, 2017 Published: March 24, 2017
Targeting CD47 efficiently enhances macrophage phagocytosis in both physiological and pathological conditions. Anti-CD47 antibodies have been shown to inhibit the progression of several types of cancer. However, the mechanism of anti-CD47 monoclonal antibody (mAb) treatment remains controversial. In this study, we confirmed that CD47 protein is highly expressed in ovarian cancer, and is correlated with poor clinical characteristics and prognosis. CD47 knockdown in the ovarian cancer cell line, SK-OV-3, promoted phagocytosis by macrophages in vitro and inhibited tumor growth in vivo. These data combined suggest that CD47 inhibition is a potential strategy for cancer treatment. Using an anti-CD47 mAb, we found that CD47 inhibition in both SK-OV-3 cells and primary cancer cells was able to recapitulate our knockdown results and led to an increase in the number of infiltrating macrophages. In addition, the CD133+ tumor initiating cells expressed a high level of CD47, and anti-CD47 mAb treatment was able to trigger the phagocytosis of this cell population. In conclusion, our results indicate that CD47 inhibits macrophage phagocytosis of ovarian cancer cells, and down-regulation of CD47 or inhibiting CD47 by mAb was able to reverse the negative effect. Thus, CD47 antibody therapy may be a promising strategy to treat ovarian cancer.
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