Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (p<0.001) MUC13 expression in non-metastatic colon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (p<0.05) higher cytoplasmic and nuclear MUC13 expression compared with non-metastatic colon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer.

[1]  H. Aburatani,et al.  MUC13 Mucin Augments Pancreatic Tumorigenesis , 2011, Molecular Cancer Therapeutics.

[2]  N. Waterhouse,et al.  The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis , 2011, Gut.

[3]  M. Jaggi,et al.  Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis , 2011, Molecular Cancer Research.

[4]  A. Jemal,et al.  Global Patterns of Cancer Incidence and Mortality Rates and Trends , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[5]  R. Cardiff,et al.  The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells , 2009, Breast Cancer Research.

[6]  J. Balko,et al.  MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion. , 2009, International journal of oncology.

[7]  R. Cone,et al.  Barrier properties of mucus. , 2009, Advanced drug delivery reviews.

[8]  H. Aburatani,et al.  Expression and functions of transmembrane mucin MUC13 in ovarian cancer. , 2009, Cancer research.

[9]  V. Korolik,et al.  MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. , 2007, The Journal of clinical investigation.

[10]  B. Leggett,et al.  The MUC13 cell surface mucin is highly expressed by human colorectal carcinomas. , 2006, Human pathology.

[11]  H. Aburatani,et al.  Overexpression of MUC13 is associated with intestinal‐type gastric cancer , 2005, Cancer science.

[12]  L. Packer,et al.  Expression of the cell surface mucin gene family in adenocarcinomas. , 2004, International journal of oncology.

[13]  J. Meza,et al.  Inhibition of MUC4 Expression Suppresses Pancreatic Tumor Cell Growth and Metastasis , 2004, Cancer Research.

[14]  G. Sutherland,et al.  MUC13, a Novel Human Cell Surface Mucin Expressed by Epithelial and Hemopoietic Cells* , 2001, The Journal of Biological Chemistry.

[15]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[16]  A. Leibovitz,et al.  Classification of human colorectal adenocarcinoma cell lines. , 1976, Cancer research.

[17]  L. Tanoue Cancer Statistics, 2011: The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths , 2012 .