CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis.
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.
['Liu|Ran|R|', 'Wei|Huiting|H|', 'Gao|Peng|P|', 'Yu|Hu|H|', 'Wang|Ke|K|', 'Fu|Zheng|Z|', 'Ju|Baohui|B|', 'Zhao|Meng|M|', 'Dong|Shangwen|S|', 'Li|Zhijun|Z|', 'He|Yifeng|Y|', 'Huang|Yuting|Y|', 'Yao|Zhi|Z|']
D000818:Animals D000911:Antibodies, Monoclonal D000970:Antineoplastic Agents D014408:Biomarkers, Tumor D051928:CD47 Antigen D045744:Cell Line, Tumor D018450:Disease Progression D005260:Female D006801:Humans D007167:Immunotherapy D053208:Kaplan-Meier Estimate D008264:Macrophages D051379:Mice D008807:Mice, Inbred BALB C D010051:Ovarian Neoplasms D010587:Phagocytosis D019139:Tumor Escape D023041:Xenograft Model Antitumor Assays
CD47 ovarian cancer macrophage phagocytosis monoclonal antibody