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

Gastroenterology. 2001 Dec;121(6):1339-47. doi: 10.1053/gast.2001.29691.


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.

MeSH terms

  • Adenocarcinoma / blood supply*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism
  • Female
  • Gene Expression*
  • Humans
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Lymphokines / genetics
  • Lymphokines / metabolism
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / metabolism
  • Up-Regulation
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Isoenzymes
  • Lymphokines
  • Membrane Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone