title: Inducible nitric oxide synthase expression in human colorectal cancer: correlation with tumor angiogenesis.
abstract: To investigate the potential involvement of the nitric oxide (NO) pathway in colorectal carcinogenesis, we correlated the expression and the activity of inducible nitric oxide synthase (iNOS) with the degree of tumor angiogenesis in human colorectal cancer. Tumor samples and adjacent normal mucosa were obtained from 46 surgical specimens. Immunohistochemical expression of iNOS, vascular endothelial growth factor (VEGF), and CD31 was analyzed on paraffin-embedded tissue sections. iNOS activity and cyclic GMP levels were assessed by specific biochemical assays. iNOS protein expression was determined by Western blot analysis. iNOS and VEGF mRNA levels were evaluated using Northern blot analysis. Both iNOS and VEGF expressions correlated significantly with intratumor microvessel density (r(s) = 0.31, P = 0.02 and r(s) = 0.67, P < 0.0001, respectively). A significant correlation was also found between iNOS and VEGF expression (P = 0.001). iNOS activity and cyclic GMP production were significantly higher in the cancer specimens than in the normal mucosa (P < 0.0001 and P < 0.0001, respectively), as well as in metastatic tumors than in nonmetastatic ones (P = 0.002 and P = 0.04, respectively). Western and Northern blot analyses confirmed the up-regulation of the iNOS protein and gene in the tumor specimens as compared with normal mucosa. NO seems to play a role in colorectal cancer growth by promoting tumor angiogenesis.
authors.affiliation: Department of General Surgery, Medical School, University of Florence, Florence, Italy. cianchif@mail.unifi.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Cianchi
authors.forename: Camillo
authors.initials: C
authors.lastname: Cortesini
authors.forename: Ornella
authors.initials: O
authors.lastname: Fantappiè
authors.forename: Luca
authors.initials: L
authors.lastname: Messerini
authors.forename: Nicola
authors.initials: N
authors.lastname: Schiavone
authors.forename: Alfredo
authors.initials: A
authors.lastname: Vannacci
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.forename: Cosimo
authors.initials: C
authors.lastname: Marzocca
authors.forename: Federico
authors.initials: F
authors.lastname: Perna
authors.forename: Roberto
authors.initials: R
authors.lastname: Mazzanti
authors.forename: Paolo
authors.initials: P
authors.lastname: Bechi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015152:Blotting, Northern; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics; D008222:Lymphokines / Q000032:analysis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D015703:Antigens, CD; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006152:Cyclic GMP; D015232:Dinoprostone