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.
Highlights
Ovarian cancer is the most lethal gynecological malignancy, and ranks fifth in female cancer-related deaths
The CD133+ tumor initiating cells expressed a high level of CD47, and anti-CD47 monoclonal antibody (mAb) treatment was able to trigger the phagocytosis of this cell population
In agreement with a previous study [9], we found that CD47 was highly expressed in ovarian cancer and was associated with poor clinical characteristics and prognosis
Summary
Ovarian cancer is the most lethal gynecological malignancy, and ranks fifth in female cancer-related deaths. Ovarian cancer accounts for up to 3% of malignant diseases in women, and the mortality of this disease accounts for up to 5% [1]. Ovarian cancer is often asymptomatic at early stages. Approximately 80% of patients are already at the advanced stages of the disease when diagnosed [2]. Mortality is highly related to metastasis-related complications, such as cachexia and multiple organ dysfunction syndromes. The elucidation of the mechanisms underlying ovarian cancer metastasis and the strategies to prevent this process are needed in order to improve treatment of ovarian cancer
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