Abstract 296: The expression and potential role of MUC7 in pancreatic adenocarcinoma
Authors: Neeley A. Remmers, Stephanie K. Bunt, Paul M. Grandgenett, Fang Yu, Michael A. Hollingsworth
Journal: Cancer Research (2012)

Abstract Human mucin 7 (MUC7) is the smallest of the mucin core proteins at 39 kD and its fully glycosylated form ranges from 125-250 kD. This secreted, non-gel forming mucin is normally expressed by the mucousal and serosal salivary glands and sub-mucosal glands in the lower respiratory tract. Recently MUC7 has been observed to be expressed in such diseases as allergic-asthma, COPD, cystic fibrosis and bladder cancer. The tandem repeat domain consists of 5-6 repeats of a 23 amino acid sequence, which contains 3 SEA domains which may serve as sites of auto-cleavage. Our immunohistochemical studies of pancreatic adenocarcionoma revealed that MUC7 was expressed in over 50% of primary tumors, liver metastases, and lymph node metastases. MUC7 was found to be primarily expressed by the immune cells in the lymph node metastases rather than tumor cells. In contrast, MUC7 was not expressed by infiltrating immune cells in primary tumors and liver metastases, but it was present in the tumors themselves. Further characterization of the immune cells expressing MUC7 in the lymph nodes (by means of immunofluorescence and flow cytometry) revealed that the majority were macrophages and myeloid-derived suppressor cells together with a small population of dendritic cells. MUC7 has been posited to play a role in inflammation. This function is likely due to a unique histatin-like domain allowing it to bind numerous microbes to promote their clearance.MUC7 has been shown to be upregulated by IL-1β, IL-4, IL-13, TNF-α, LPS, and EGF in inflammed airways, and its minimal proximal promoter contains binding sites for NF-κB, AP1 and STAT transcription factors; all of which are involved in promoting inflammation. We found that MUC7 expression was up-regulated in the pancreatic cancer cell line Hs766T and the breast cancer cell line BT474 upon incubation with Th1 cytokines IFN-γ, IL-1β and TNF-α and the Th2 cytokines IL-4, IL-10 and IL-13. MUC7 over-expression was achieved in a time-dependent manner when incubated with the Th1 cytokines; however immediate and sustained expression was observed when cells were treated with the Th2 cytokines. Global gene expression by microarray was evaluated on samples of primary and metastatic pancreatic adenocarcinoma that expressed or did not express MUC7 to identify candidate genes affected by MUC7 expression. The microarray data revealed that a number of genes involved in tissue remodeling and inflammation were differentially regulated by MUC7 expressing tumors. Together, the data from the analyses presented here led us to propose that MUC7 has a role in establishing a pro-tumorigenic microenvironment through enhancing the Th2 inflammatory response and aiding in tissue remodeling. 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 296. doi:1538-7445.AM2012-296