title: CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis.
abstract: 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.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department 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.
authors.forename: Huiting
authors.initials: H
authors.lastname: Wei
authors.affiliation: University of the District of Columbia, Washington D.C., 20008, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300040, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Yu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300040, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Ju
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300040, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Shangwen
authors.initials: S
authors.lastname: Dong
authors.affiliation: Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Renji Hospital, Shanghai, 200127, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: He
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300040, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department 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.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis; D051928:CD47 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051928:CD47 Antigen; C497894:CD47 protein, human
keywords: CD47; macrophage; monoclonal antibody; ovarian cancer; phagocytosis