Inducible nitric oxide synthase expression in human colorectal cancer -: Correlation with tumor angiogenesis

被引:130
作者
Cianchi, F
Cortesini, C
Fantappiè, O
Messerini, L
Schiavone, N
Vannacci, A
Nistri, S
Sardi, I
Baroni, G
Marzocca, C
Perna, F
Mazzanti, R
Bechi, P
Masini, E
机构
[1] Univ Florence, Sch Med, Dept Gen Surg, Florence, Italy
[2] Univ Florence, Sch Med, Dept Internal Med, Florence, Italy
[3] Univ Florence, Sch Med, Dept Human Pathol & Oncol, Florence, Italy
[4] Univ Florence, Sch Med, Dept Expt Pathol & Oncol, Florence, Italy
[5] Univ Florence, Sch Med, Dept Preclin & Clin Pharmacol, Florence, Italy
[6] Univ Florence, Sch Med, Dept Anat Histol & Forens Med, Florence, Italy
[7] Univ Florence, Sch Med, Dept Pediat, Oncohematol Unit, Florence, Italy
关键词
D O I
10.1016/S0002-9440(10)63876-X
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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页码:793 / 801
页数:9
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