%0 Journal Article
%T Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer
%A Vishnu C Ramani
%A Leah Hennings
%A Randy S Haun
%J BMC Cancer
%D 2008
%I BioMed Central
%R 10.1186/1471-2407-8-373
%X The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.Pancreatic cancer is one of the deadliest of all human cancers, resulting in more than 30,000 deaths per year in the United States alone, and continues to be a major health problem in terms of detection as well as treatment. Pancreatic cancer is highly invasive and is characterized by early metastasis. Tumor invasion and metastasis is a multi-step process involving several key cellular events [1]. Among the many events leading to tumor dissemination and metasta
%U http://www.biomedcentral.com/1471-2407/8/373