Abstract 1819: A MUC1-C oncoprotein soluble decoy receptor effectively suppresses the growth of human breast cancer cells

Abstract

Abstract The Mucin 1 (MUC1) transmembrane glycoprotein is aberrantly overexpressed by most human breast carcinomas and contributes to the malignant phenotype. MUC1 is expressed as two subunits (MUC1-N and MUC1-C) that form a stable heterodimer at the cell surface. MUC1-N is shed to contribute to a protective physical barrier, leaving the oncogenic MUC1-C subunit at the cell surface as a putative receptor for signaling the presence of stress to the interior of the cell. As shown for the VEGF receptor TRAP, aflibercept, a potential approach for blocking MUC1-C function is to generate a soluble decoy receptor by fusing the MUC1-C extracellular domain to an Ig constant (Fc) region. The present studies demonstrate that in vitro treatment of human ZR-75-1 breast carcinoma cells with the MUC1-C soluble decoy receptor is associated with a dose-dependent induction of cell death. Similar findings were obtained with human MCF-7 breast cancer cells. To explore the potential of the MUC1-C soluble decoy receptor as an anti-cancer agent, we evaluated its ability to block the growth of breast cancer cells in subcutaneous tumor xenograft models growing in nude mice. Administration of the MUC1-C soluble decoy receptor to nude mice bearing established ZR-75-1 breast tumor xenografts was associated with a dose-dependent loss of tumorigenicity and prolonged tumor regressions after completing therapy. Taken together, these findings demonstrate that targeting the MUC1-C oncoprotein with a soluble decoy receptor is effective in inducing death of human breast cancer cells in vitro and in tumor models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1819. doi:1538-7445.AM2012-1819