title: Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumour cell invasion.
abstract: The present study investigates the role of nitric oxide and the involvement of nitric oxide synthase II isoform on the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29. HRT-18 cells, which constitutively express nitric oxide synthase II mRNA were three-fold more invasive in a Matrigel invasion assay than nitric oxide synthase II mRNA negative HT-29 cells. Treatment of HT-29 cells with the nitric oxide donor Deta NONOate (50 nM) as well as induction of nitric oxide synthase II mRNA and production of endogenous nitric oxide by inflammatory cytokines (IFN-gamma and IL-1alpha) increased the invasiveness of HT-29 cells by approximately 40% and 75%, respectively. In HT-29 cells nitric oxide synthase II mRNA was also induced in co-culture with human monocytes. The invasiveness of HRT-18 cells and stimulated HT-29 cells was partly inhibited by the nitric oxide synthase II inhibitor 1400 W. These results show that nitric oxide increases the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29, and the involvement of nitric oxide synthase II isoform in tumour cell invasion. Therefore, the production of nitric oxide and secretion of pro-inflammatory cytokines by tumour-associated macrophages, which in turn induce nitric oxide synthase II isoform in tumour cells, promotes tumour cell invasiveness.
authors.affiliation: Institute of Pathology, Charité Hospital, Humboldt University, Schumannstr 20/21, D-10117 Berlin, Germany. antje.siegert@charite.de
authors.forename: A
authors.initials: A
authors.lastname: Siegert
authors.forename: C
authors.initials: C
authors.lastname: Rosenberg
authors.forename: W D
authors.initials: WD
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.forename: S
authors.initials: S
authors.lastname: Hauptmann
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000578:Amidines / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009603:Nitroso Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000578:Amidines; D001596:Benzylamines; D007375:Interleukin-1; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009603:Nitroso Compounds; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II