Role of CD47 in triple negative breast cancer

Abstract

CD47 is a ubiquitously expressed cell surface receptor for thrombospondin-1 and SIRPα. High expression of CD47 on several types of cancer cells has been identified as a 'don't eat me signal' that inhibits their killing by macrophages or NK cells. Conversely, the CD47 antibody B6H12 blocks SIRPα binding and enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance is independent of SIRPα signaling. Cancer stem cells (CSCs) have been reported to express elevated CD47 levels, but the role of CD47 in regulating CSC function has not been examined. Subpopulations enriched in breast CSCs were isolated from the triple negative MDA-MB-231 cell line by selection for weak substrate adhesion or by sorting for CD44++ and CD24-- expression. Treatment with B6H12 inhibited proliferation of the CSCs and suppressed their asymmetric cell division. Global analysis of gene expression of CSCs treated with B6H12 showed up-regulation of tumor suppressor, apoptotic g...