Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the vasculature of human pancreatic tumor biopsies.

Abstract

Cellular nitric oxide (NO) synthesis determines whether NO has cytoprotective or cytotoxic effects at anatomic sites; thus it is important to identify potential NO synthase isoforms in tumor tissue and tumor cell lines which might be involved in tumor development or destruction. Incubation of human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, CaPan-2) with cytokines resulted in increased NO formation, indicating the existence of the NOS2 isoform. This was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, we identified the presence of the endothelium-derived NOS isoform 3 by RT-PCR analysis and immunohistochemistry in normal and pancreatic tumor biopsies. NOS3 was markedly overexpressed in the vasculature of the tumor tissue. RT-PCR analysis of tumor biopsies identified NOS isoform 2 mRNA in 60% of cases, but western blot analysis or immunohistochemistry scored negative for this isoform. It is noteworthy that the NOS enzyme activity in pancreatic tumor cell lines and tumor biopsies was inhibited by EGTA by approximately 30% and 65%, respectively. Our results suggest that increased endothelium-derived NOS isoform 3 expression in pancreatic adenocarcinomas regulates blood flow and is therefore involved in the vascularization and neovascularization of human pancreatic tumors.

• Authors: A K Nussler, S Gansauge, F Gansauge, U Fischer, U Butzer, P G Kremsner, H G Beger
• Journal: Langenbeck's archives of surgery (Langenbecks Arch Surg) Vol. 383 Issue 6 Pg. 474-80 (Dec 1998) ISSN: 1435-2443 [Print] Germany
• PMID: 9921950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• RNA, Messenger
• Intercellular Adhesion Molecule-1
• Nitric Oxide
• Egtazic Acid
• NOS3 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III

Topics

• Adenocarcinoma (blood supply, metabolism)
• Biopsy
• Blood Vessels (enzymology)
• Blotting, Western
• Egtazic Acid (pharmacology)
• Humans
• Immunohistochemistry
• Intercellular Adhesion Molecule-1 (metabolism)
• Isoenzymes (metabolism)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III
• Pancreas (enzymology, metabolism)
• Pancreatic Neoplasms (blood supply, metabolism)
• Polymerase Chain Reaction
• RNA, Messenger (analysis)
• Tumor Cells, Cultured