COX-2 expression and tumor angiogenesis in colorectal cancer.

AIM Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes in metabolism of arachidonic acid, and COX-2 inhibitors demonstrate preventive effects on cancer, especially on colorectal cancer. The underlying mechanism remains unclear. The aim of this study was to illustrate the relationship between angiogenesis and COX-2 in carcinogenesis of colorectal cancer. METHODS One hundred and seventy patients with colorectal cancer were enrolled in our study from January 1993 to September 2001 in School of Oncology, Peking University. COX-2 and VEGF expression were detected with the immunohistochemistry (IHC) technique. IHC assays were carried out with the aid of tissue microarray (TMA) procedure. Specimens from 35 of these patients were examined with reverse transcriptase PCR (RT-PCR). RESULTS COX-2 and VEGF expressions were stronger in colorectal cancer than those in the corresponding normal tissues, at both protein and mRNA levels. One hundred patients were eligible for analysis after IHC assay of COX-2 and VEGF. The positive rate of VEGF was much higher in COX-2 positive group (47/85) than in COX-2 negative group (chi (2) = 4.181, P = 0.041). The result was further verified by the result of RT-PCR (chi (2) = 8.517, P = 0.003). Correlation coefficient was 0.409 after Spearman correlation analysis (P = 0.015). CONCLUSION COX-2 may be involved in the course of tumor angiogenesis of colorectal cancer and acts through VEGF.

[1]  F. Chan,et al.  Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma. , 2003, International journal of oncology.

[2]  J. Gu,et al.  Role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients' prognosis. , 2003, World journal of gastroenterology.

[3]  A. Klein-Szanto,et al.  CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. , 2003, Cancer research.

[4]  J. Sleeman,et al.  Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats. , 2003, Cancer research.

[5]  K. Subbaramaiah,et al.  Cyclooxygenase 2: a molecular target for cancer prevention and treatment. , 2003, Trends in pharmacological sciences.

[6]  F. Cianchi,et al.  Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. , 2001, Gastroenterology.

[7]  A. Ristimäki,et al.  Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  W. Ichikawa,et al.  Depth of invasion parallels increased cyclooxygenase‐2 levels in patients with gastric carcinoma , 2001, Cancer.

[9]  K. Chayama,et al.  Clinical Significance of Vascular Endothelial Growth Factor C Expression and Angiogenesis at the Deepest Invasive Site of Advanced Colorectal Carcinoma , 2001, Oncology.

[10]  M. Tachibana,et al.  Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[11]  M. Dewhirst,et al.  Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. , 2000, Journal of the National Cancer Institute.

[12]  A. Levine,et al.  Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. , 2000, The Journal of urology.

[13]  A. Weeraratna,et al.  Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. , 2000, Cancer research.

[14]  T. Tsuruo,et al.  Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer , 2000, British Journal of Cancer.

[15]  S. Prescott.  Is cyclooxygenase-2 the alpha and the omega in cancer? , 2000, The Journal of clinical investigation.

[16]  S. Dey,et al.  Host cyclooxygenase-2 modulates carcinoma growth. , 2000, The Journal of clinical investigation.

[17]  Y. Doki,et al.  Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  E. Fosslien.  Biochemistry of Cyclooxygenase (COX)-2 Inhibitors and Molecular Pathology of COX-2 in Neoplasia , 2000, Critical reviews in clinical laboratory sciences.

[19]  R. DuBois,et al.  The role of cyclooxygenases in inflammation, cancer, and development , 1999, Oncogene.

[20]  T. Tsuruo,et al.  Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522 , 1999, British Journal of Cancer.

[21]  A. Dannenberg,et al.  Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2. , 1999, Seminars in oncology.

[22]  A. Ristimäki,et al.  Expression of cyclooxygenase-2 in human lung carcinoma. , 1998, Cancer research.

[23]  R. DuBois,et al.  Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells , 1998, Cell.

[24]  J. Folkman,et al.  Vasculogenesis, Angiogenesis, and Growth Factors: Ephrins Enter the Fray at the Border , 1998, Cell.

[25]  K. Seibert,et al.  Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. , 1998, Cancer research.

[26]  J. Brown,et al.  The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan. , 1997, Cancer research.

[27]  R. DuBois,et al.  Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. DuBois,et al.  Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 , 1995, Cell.

[29]  R. Coffey,et al.  Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. , 1994, Gastroenterology.

[30]  J. Folkman.  What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[31]  Bandaru,et al.  Advances in Brief Evaluation of Cyclooxygenase-2 Inhibitor for Potential Chemopreventive Properties in Colon Carcinogenesis ' , 2006 .

[32]  L. Ellis.  A targeted approach for antiangiogenic therapy of metastatic human colon cancer. , 2003, The American surgeon.

[33]  T. Westfall,et al.  ALTERATIONS IN THE , 1985 .