Liver, Pancreas, and Biliary TractClaudin-4: A new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin☆,☆☆,★
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Materials and cell lines
Human tissue from patients with histologically verified ductal adenocarcinoma of the pancreas, tumor tissues of different origin, human pancreatic tissue from organ donors, and chronic pancreatitis tissues were provided by the Department of Surgery at the University of Ulm and by the Hungarian Academy of Sciences (Budapest, Hungary). All tissues were obtained after approval by local ethics committees.
The human pancreatic cancer cell lines were obtained from the following suppliers: PANC-1 and
Expression pattern of Claudin-4 in pancreatic cancer and normal tissues
Northern blot analyses showed that claudin-4 expression was very weak or absent in all normal pancreas (n = 9) and chronic pancreatitis (n = 9) tissues. In contrast, it was strongly overexpressed in 24 of 31 pancreatic cancer tissues (Figure 1).
Discussion
CPE is considered the virulence factor responsible for the symptoms of C. perfringens strain A food poisoning and some cases of non–food-borne human gastrointestinal diseases, e.g., antibiotic-associated diarrhea.23 CPE-induced injury of intestinal epithelial cells, morphologically characterized by bleb balloon formation, is initiated by binding to receptors such as CPE-R.14, 24 The C-terminal domain of CPE has been shown to be responsible for high-affinity binding to the CPE-R1; the N-terminal
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Supported by grants of the Deutsche Forschungsgemeinschaft (SFB 518/Project B1), the European Community (BMH4-CT98-3085), and the National Institutes of Health (AI19844-17).
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Address requests for reprints to: Thomas M. Gress, M.D., Universität Ulm, Abteilung Innere Medizin I, Robert-Koch-Strasse 8, 89081 Ulm, Germany. e-mail: [email protected]; fax: (49) 731-500-24302.
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Patrick Michl and Malte Buchholz contributed equally to this work.