title: Expression of neutral endopeptidase (NEP/CD10) on pancreatic tumor cell lines, pancreatitis and pancreatic tumor tissues.
abstract: Neutral endopeptidase (NEP/CD10) is a cell surface zinc metalloprotease cleaving peptide bounds on the amino terminus of hydrophobic amino acids and inactivating multiple physiologically active peptides. Loss or decrease in NEP/CD10 expression have been reported in many types of malignancies, but the role of NEP/CD10 in pancreatic carcinoma has not yet been identified. Using real-time RT-PCR, flow cytometry as well as immunohistochemistry, NEP/CD10 expression was quantified in both pancreatic carcinoma cell lines and in tumor specimens obtained from patients with primary pancreatic carcinomas. Three out of 8 pancreatic carcinoma cell lines exhibit heterogeneous NEP/CD10 expression levels: PATU-8988T expressed the highest NEP/CD10 levels, whereas HUP-T4 and HUP-T3 cells showed a moderate to low NEP/CD10 expression. NEP/CD10 immunoreactivity was found in 6 of 24 pancreatic ductal adenocarcinomas, but also in 3 of 6 tissues of patients with chronic pancreatitis. NEP/CD10 expression in pancreatic tumor lesions and cell lines was not associated with tumor grading and staging. Treatment of PATU-8988T cells with the histone deacetylase inhibitors sodium butyrate and valproic acid induced an increase of NEP/CD10 expression. This was accompanied by a reduced cell proliferation rate of PATU-8988T cells, which was increased by the addition of the enzyme activity inhibitors phosphoramidon and thiorphan. Thus, NEP/CD10 is differentially expressed in pancreatic tumors and might be involved in the proliferative activity of pancreatic cancer cells. However, further studies are needed to provide more detailed information of the role of NEP/CD10 under physiological and pathophysiological conditions of the pancreas.
authors.affiliation: Institute of Medical Immunology, Martin-Luther University Halle Wittenberg, Germany.
authors.forename: Mabruk
authors.initials: M
authors.lastname: Erhuma
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Tarek
authors.initials: T
authors.lastname: Mustafa
authors.forename: Jens
authors.initials: J
authors.lastname: Wulfänger
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Jürgen
authors.initials: J
authors.lastname: Langner
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Astrid
authors.initials: A
authors.lastname: Kehlen
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D010195:Pancreatitis / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D015260:Neprilysin