Abstract 4963: The dynamic change of CD47 expression promotes tumor burden, metastases and resistance of breast cancer cells to radiotherapy.

Immune tolerance towards malignant cells is responsible for tumor progression and metastases. Despite their immunogenicity, cancer cells developed sophisticated mechanisms by which they are able to neutralize and/or evade the immune-surveillance. Recently, the overexpression of CD47 has been suggested to participate in the immune escape mechanism in several malignant diseases. However, mechanisms involved in CD47 expression, especially in response to anticancer agents are not yet known. In this study, we found that CD47 is overexpressed in breast cancer cells (MCF7, MDA-231, 4T1 cells) compared to non-transformed breast epithelial cells (MCF10A) and this expression is further enhanced in response to radiation (5Gy). The expression of CD47 was found to be regulated by NF-κB through a specific responsive element in the CD47 promoter as assessed by gene deletion and ChiP assays. Furthermore, using syngeneic orthotopic 4T1 mouse model, we found that CD47 is critical for both tumor burden and metastases, since anti-CD47 (100 μg/day/mice) was able to reduce tumor growth when the antibody was injected during 4T1 inoculation (day 0) or 15 th after tumor growth. Consequently, tumor size and lesions were reduced and mouse survival was increased in the presence of anti-CD47 and this effect was further enhanced with radiation (4 Gy/day for 5 days). Taken together, these data suggest that CD47 expression is a marker for tumor aggressiveness and resistance to anti-cancer agents and therefore could be a potential target to treat metastatic and recurrent tumors. Citation Format: Cheikh Menaa, Ming Fan, Hsien-Chen Lu, Aris Alexandrou, Shuaib Juma, Julian Perks, Jian Jian Li. The dynamic change of CD47 expression promotes tumor burden, metastases and resistance of breast cancer cells to radiotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4963. doi:10.1158/1538-7445.AM2013-4963