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Claudin-4: A new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin

Michl, Patrick ; Buchholz, Malte ; Rolke, Monika ; Kunsch, Steffen ; Löhr, Matthias ; McClane, Bruce ; Tsukita, Shoichiro ; Leder, Gerhard ; Adler, Guido ; Gress, Thomas M.

Gastroenterology (New York, N.Y. 1943), 2001-09, Vol.121 (3), p.678-684 [Periódico revisado por pares]

New York, NY: Elsevier Inc

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Título:
Claudin-4: A new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin
Autor: Michl, Patrick ; Buchholz, Malte ; Rolke, Monika ; Kunsch, Steffen ; Löhr, Matthias ; McClane, Bruce ; Tsukita, Shoichiro ; Leder, Gerhard ; Adler, Guido ; Gress, Thomas M.
Assuntos: Adenocarcinoma - drug therapy ; Adenocarcinoma - physiopathology ; Animals ; Antineoplastic agents ; Biological and medical sciences ; Carcinoma, Pancreatic Ductal - drug therapy ; Carcinoma, Pancreatic Ductal - physiopathology ; Chemotherapy ; Claudin-4 ; Dose-Response Relationship, Drug ; Enterotoxins - pharmacology ; Gene Expression Regulation, Neoplastic ; Humans ; In Vitro Techniques ; Medical sciences ; Membrane Proteins - genetics ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - physiopathology ; Pharmacology. Drug treatments ; RNA, Messenger - analysis ; Tight Junctions - physiology ; Transforming Growth Factor beta - pharmacology ; Transplantation, Heterologous ; Tumor Cells, Cultured
É parte de: Gastroenterology (New York, N.Y. 1943), 2001-09, Vol.121 (3), p.678-684
Descrição: Background & Aims: Recently, several members of the claudin family have been identified as integral constituents of tight junctions. Using expression profiling, we previously found claudin-4 to be overexpressed in pancreatic cancer. Because claudin-4 has been described as a receptor for the cytotoxic Clostridium perfringens enterotoxin (CPE), we investigated the effect of CPE on pancreatic cancer cells. Methods: Expression of claudin-4 was analyzed by Northern blots. In vitro toxicity of CPE was determined by trypan blue exclusion and the 86Rb-release assay. The in vivo effect of CPE was studied in claudin-4–expressing nude mouse xenografts of the Panc-1 cell line. Results: Expression analyses showed that claudin-4 was overexpressed in most pancreatic cancer tissues and cell lines and several other gastrointestinal tumors. CPE led to an acute dose-dependent cytotoxic effect, restricted to claudin-4–expressing cells and dependent on claudin-4 expression levels. Furthermore, transforming growth factor β was identified as a negative modulator of both claudin-4 expression and susceptibility to CPE. In vivo, intratumoral injections of CPE in Panc-1 xenografts led to large areas of tumor cell necrosis and significant reduction of tumor growth. Conclusions: Our findings suggest that targeting claudin-4–expressing tumors with CPE represents a promising new treatment modality for pancreatic cancer and other solid tumors. GASTROENTEROLOGY 2001;121:678-684
Editor: New York, NY: Elsevier Inc
Idioma: Inglês

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Claudin-4: A new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin

Michl, Patrick ; Buchholz, Malte ; Rolke, Monika ; Kunsch, Steffen ; Löhr, Matthias ; McClane, Bruce ; Tsukita, Shoichiro ; Leder, Gerhard ; Adler, Guido ; Gress, Thomas M.

New York, NY: Elsevier Inc

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