Cyclooxygenase-2 expression and angiogenesis in colorectal cancer

World J Gastroenterol. 2003 Jun;9(6):1237-40. doi: 10.3748/wjg.v9.i6.1237.

Abstract

Aim: Cyclooxygenase-2 is involved in a variety of important cellular functions, including cell growth and differentiation, cancer cell motility and invasion, angiogenesis and immune function. However, the role of cyclooxygenase-2 as an angiogenic factor in colorectal cancer tissue is still unclear. We investigated the relationship between cyclooxygenase-2 and angiogenesis by analyzing the expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD).

Methods: The expression of cyclooxygenase-2, VEGF, as well as MVD was detected in 128 cases of colorectal cancer by immunohistochemical staining. The relationship between the cyclooxygenase-2 and VEGF expression and MVD was evaluated. Our objective was to determine the effect of cyclooxygenase-2 on the angiogenesis of colorectal cancer tissue.

Results: Among 128 cases of colorectal cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %), respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7 (standard deviation, 19.8). The expression of cyclooxygenase-2 was correlated significantly with the depth of invasion, stage of disease, metastasis (lymph node and liver), VEGF expression and MVD. Patients in T3-T4, stage III-IV and with metastasis had much higher expression of cyclooxygenase-2 than patients in T1-T2, stage I-II and without metastasis (P<0.05). The positive expression rate of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in the cyclooxygenase-2 negative group (18.4 %, P<0.05). Also, the microvessel count (56+/-16) in cyclooxygenase-2 positive group was significantly higher than that in cyclooxygenase-2 negative group (43+/-12, P<0.05). The microvessel count in tumors with positive cyclooxygenase-2 and VEGF was the highest (60+/-18, 41-142, P<0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF was the lowest (39+/-16, 23-68, P<0.05).

Conclusion: Cyclooxygenase-2 may be associated with tumor progression by madulating the angiogenesis in colorectal cancer tissue and used as a possible biomarker.

MeSH terms

  • Adenocarcinoma / blood supply*
  • Adenocarcinoma / metabolism*
  • Adult
  • Aged
  • Blood Vessels / pathology
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / metabolism*
  • Cyclooxygenase 2
  • Endothelial Growth Factors / metabolism
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Isoenzymes / metabolism*
  • Lymphokines / metabolism
  • Male
  • Membrane Proteins
  • Microcirculation
  • Middle Aged
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Lymphokines
  • Membrane Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases