Abstract 1481: MUC13 expression enhances colon cancer progression

Abstract

Abstract Background: Mucin, a family of high molecular weight glycoprotein has been implicated in a variety of cancers. MUC13 is a newly identified transmembrane mucin which has shown deregulated expression in gastric and ovarian cancers. However, limited information is available about the role of MUC13 in colon cancer progression. The present study investigated the expression profile, clinical relevance and functional significance of MUC13 expression in colon cancer progression. Materials and Methods: The MUC13 expression profile was determined by immunohistochemical (IHC) analysis using a novel MUC13 monoclonal antibody (PPZ0020) on a panel of colon cancer tissue microarrays containing non-malignant, colon cancer and liver metastasis tissue samples. Colon cancer cell lines which showed faint (SW480) and high (SW620) MUC13 expression were selected for over-expression and knockdown experiments, respectively, to determine the functional role of MUC13 in colon cancer progression. Functional studies, such as cell proliferation, colony formation, cell migration and cell invasion assays were performed in stable clones. The levels of Sonic hedehog (Shh), B cell moloney murine leukemia virus integration site 1 (Bmi-1) and Matrix metalloproteinase 1 (MMP1) were determined using real time PCR, Western blot and flow cytometry analyses. Results: Differential expression and sub-cellular localization of MUC13 was observed in cancerous and non-malignant tissues. MUC13 IHC analysis showed significantly higher membranous and cytoplasmic MUC13 expression in colon cancer and liver metastasis tissues compared to non-malignant tissue samples. Interestingly, liver metastasis tissue samples showed significantly higher nuclear MUC13 expression in addition to high membranous and cytoplasmic expression. The over-expression of MUC13 enhanced cell proliferation, colony formation, cell migration and cell invasion. In contrast, knockdown of MUC13 resulted in reduced cell proliferation, colony formation, cell migration and cell invasion. Additionally, over-expression of MUC13 increased the expression level of metastatic associated proteins such as Shh, Bmi-1 and MMP1 while knockdown of MUC13 decreased the expression level of these proteins. Conclusions: The present study suggests two important outcomes pertaining to MUC13 in colon cancer: (1) The aberrant expression of MUC13 could serve as a potential diagnostic/prognostic molecular tool for clinical use, and (2) MUC13 over-expression may enhance colon cancer carcinogenesis via modulation of metastatic proteins Bmi-1, Shh and MMP1. These data suggest a potential role of MUC13 in colon cancer progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2011-1481