CD47 is highly expressed in gliomas and targeting CD47 is a promising therapeutic strategy

Abstract

Gliomas are very malignant brain tumors that are difficult to treat. CD47 is an antiphagocytic molecule that binds to SIPRα on phagocytes. It is overexpressed on the plasma membranes of multiple human tumor cell types and is an important diagnostic and prognostic biomarker in many types of cancer. However, the association between CD47 protein expression in glioma tissue and clinicopathological stage has not been investigated in detail. A total of 80 surgical glioma specimens were stained with anti-CD47 antibody to assess the relationship between CD47 protein expression and clinicopathological stage of the glioma. Wound healing assays were performed to analyze the influence of CD47 on the migration and invasion of glioma cells, and near-infrared fluorescence localization assays in a U-87 MG-bearing xenograft model were used to determine the distribution of anti-CD47 antibody in vivo. MTT assays and administration of anti-CD47 to a U251-bearing xenograft model were used to analyze the inhibitory effects of the antibody on gliomas. CD47 expression was higher in high-grade gliomas than in low-grade gliomas, and high CD47 expression was positively correlated with histology and tumor clinicopathological stage. CD47 over-expression promoted the growth and motility of two glioma cell lines (U-87 MG and U251) and a laboratory-developed anti-CD47 antibody accumulated at the glioma site. Proliferation of U251 and U-87 MG cells was not significantly inhibited by the anti-CD47 antibody in vitro, but the antibody significantly inhibited U251 growth in vivo. It also enhanced inhibition capacity by Taxol. Our results suggest that CD47 plays a critical role in the progression of gliomas from stage I to IV and may be a potential target for the treatment of gliomas. CD47 appears to play a critical role in the progression of gliomas from stage I to IV and an anti-CD47 antibody prepared in the laboratory may inhibit the growth of gliomas.