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Gastroenterology. 2001 Dec;121(6):1339-47.

Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.

Author information

  • 1Department of General Surgery, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. cianchif@mail.unifi.it

Abstract

BACKGROUND & AIMS:

Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer.

METHODS:

Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay.

RESULTS:

The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03).

CONCLUSIONS:

COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.

PMID:
11729113
[PubMed - indexed for MEDLINE]
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