Cyclooxygenase-2 Expression in Human Esophageal Carcinoma

Tumor Biology

Cyclooxygenase-2 Expression in Human Esophageal Carcinoma¹

Katja C. Zimmermann, Mario Sarbia², Artur-Aron Weber, Franz Borchard, Helmut E. Gabbert and Karsten Schrör

Institut für Pharmakologie [K. C. Z., A-A. W., K. S.] and Institut für Pathologie [M. S., H. E. G.], Heinrich-Heine-Universität, 40225 Düsseldorf, and Institut für Pathologie, Klinikum Aschaffenburg, 63739 Aschaffenburg [F. B.], Germany

On the basis of epidemiological observations that nonsteroidalanti-inflammatory drugs reduce the risk of esophageal carcinoma,we studied the expression of cyclooxygenase-2 (COX-2) in esophagealsquamous cell carcinomas (SCCs; n = 172) and in esophageal adenocarcinomas(ADCs; n = 27). Using immunohistochemistry, we observed COX-2expression in 91% of the SCCs and in 78% of the ADCs. Westernblot analysis showed enhanced expression of the COX-2 proteinin some tumors as compared with normal esophageal squamous epithelium,whereas similar amounts of the COX-1 protein were found in normaland cancerous tissues. COX expression was also studied in twoesophageal cancer cell lines (OSC-1 and OSC-2) to evaluate thefunctional relevance of COX-2-derived prostaglandins (PGs).OSC-2 cells expressed COX-2 but not COX-1, whereas OSC-1 cellsexpressed high levels of COX-1 but showed only a very weak COX-2expression. Accordingly, PGE₂ synthesis was 600 times higherin the OSC-2 cells as compared with the OSC-1 cells. Treatmentof OSC-2 cells with the selective COX-2 inhibitors flosulideand NS-398 concentration dependently suppressed PGE₂ synthesisand proliferation and also induced apoptosis. In contrast, noeffect of the COX-2 inhibitors was seen in OSC-1 cells. Ourdata demonstrate that COX-2 is expressed in the majority ofesophageal SCCs and ADCs and that COX-2-derived PGs play animportant role in the regulation of proliferation and apoptosisof esophageal tumor cells. It is concluded that inhibition ofCOX-2 may be useful in the therapy of esophageal cancer.

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Selective Inhibition of Cyclooxygenase-2 Suppresses Growth and Induces Apoptosis in Human Esophageal Adenocarcinoma Cells
Cancer Res., October 1, 2000; 60(20): 5767 - 5772.
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R. Masunaga, H. Kohno, D. K. Dhar, S. Ohno, M. Shibakita, S. Kinugasa, H. Yoshimura, M. Tachibana, H. Kubota, and N. Nagasue
Cyclooxygenase-2 Expression Correlates with Tumor Neovascularization and Prognosis in Human Colorectal Carcinoma Patients
Clin. Cancer Res., October 1, 2000; 6(10): 4064 - 4068.
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A. Kirschenbaum, D. R. Liotta, S. Yao, X.-H. Liu, A. P. Klausner, P. Unger, E. Shapiro, I. Leav, and A. C. Levine
Immunohistochemical Localization of Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Fetal and Adult Male Reproductive Tracts
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3436 - 3441.
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T. Joki, O. Heese, D. C. Nikas, L. Bello, J. Zhang, S.-K. Kraeft, N. T. Seyfried, T. Abe, L. B. Chen, R. S. Carroll, et al.
Expression of Cyclooxygenase 2 (COX-2) in Human Glioma and in Vitro Inhibition by a Specific COX-2 Inhibitor, NS-398
Cancer Res., September 1, 2000; 60(17): 4926 - 4931.
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J. J. Y. Sung, W. K. Leung, M. Y. Y. Go, K. F. To, A. S. L. Cheng, E. K. W. Ng, and F. K. L. Chan
Cyclooxygenase-2 Expression in Helicobacter pylori-Associated Premalignant and Malignant Gastric Lesions
Am. J. Pathol., September 1, 2000; 157(3): 729 - 735.
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M. Takahashi, M. Mutoh, T. Kawamori, T. Sugimura, and K. Wakabayashi
Altered expression of {beta}-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis
Carcinogenesis, July 1, 2000; 21(7): 1319 - 1327.
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M. Li, R. Lotan, B. Levin, E. Tahara, S. M. Lippman, and X.-C. Xu
Aspirin Induction of Apoptosis in Esophageal Cancer: A Potential for Chemoprevention
Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 545 - 549.
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A.-L. Hsu, T.-T. Ching, D.-S. Wang, X. Song, V. M. Rangnekar, and C.-S. Chen
The Cyclooxygenase-2 Inhibitor Celecoxib Induces Apoptosis by Blocking Akt Activation in Human Prostate Cancer Cells Independently of Bcl-2
J. Biol. Chem., April 6, 2000; 275(15): 11397 - 11403.
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A. K. Bauer, L. D. Dwyer-Nield, and A. M. Malkinson
High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors
Carcinogenesis, April 1, 2000; 21(4): 543 - 550.
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A. Shamma, H. Yamamoto, Y. Doki, J. Okami, M. Kondo, Y. Fujiwara, M. Yano, M. Inoue, N. Matsuura, H. Shiozaki, et al.
Up-Regulation of Cyclooxygenase-2 in Squamous Carcinogenesis of the Esophagus
Clin. Cancer Res., April 1, 2000; 6(4): 1229 - 1238.
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M. T. Yip-Schneider, D. S. Barnard, S. D. Billings, L. Cheng, D. K. Heilman, A. Lin, S. J. Marshall, P. L. Crowell, M. S. Marshall, and C. J. Sweeney
Cyclooxygenase-2 expression in human pancreatic adenocarcinomas
Carcinogenesis, February 1, 2000; 21(2): 139 - 146.
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C.-J. Yuan, A. K. Mandal, Z. Zhang, and A. B. Mukherjee
Transcriptional Regulation of Cyclooxygenase-2 Gene Expression: Novel Effects of Nonsteroidal Anti-Inflammatory Drugs
Cancer Res., February 1, 2000; 60(4): 1084 - 1091.
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H. Y. Lim, H. J. Joo, J. H. Choi, J. W. Yi, M. S. Yang, D. Y. Cho, H. S. Kim, D. K. Nam, K. B. Lee, and H. C. Kim
Increased Expression of Cyclooxygenase-2 Protein in Human Gastric Carcinoma
Clin. Cancer Res., February 1, 2000; 6(2): 519 - 525.
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M. Kondo, H. Yamamoto, H. Nagano, J. Okami, Y. Ito, J. Shimizu, H. Eguchi, A. Miyamoto, K. Dono, K. Umeshita, et al.
Increased Expression of COX-2 in Nontumor Liver Tissue Is Associated with Shorter Disease-free Survival in Patients with Hepatocellular Carcinoma
Clin. Cancer Res., December 1, 1999; 5(12): 4005 - 4012.
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S. I. Mohammed, D. W. Knapp, D. G. Bostwick, R. S. Foster, K. N. M. Khan, J. L. Masferrer, B. M. Woerner, P. W. Snyder, and A. T. Koki
Expression of Cyclooxygenase-2 (COX-2) in Human Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder
Cancer Res., November 1, 1999; 59(22): 5647 - 5650.
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M. A. Molina, M. Sitja-Arnau, M. G. Lemoine, M. L. Frazier, and F. A. Sinicrope
Increased Cyclooxygenase-2 Expression in Human Pancreatic Carcinomas and Cell Lines: Growth Inhibition by Nonsteroidal Anti-Inflammatory Drugs
Cancer Res., September 1, 1999; 59(17): 4356 - 4362.
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J. Okami, H. Yamamoto, Y. Fujiwara, M. Tsujie, M. Kondo, S. Noura, S. Oshima, H. Nagano, K. Dono, K. Umeshita, et al.
Overexpression of Cyclooxygenase-2 in Carcinoma of the Pancreas
Clin. Cancer Res., August 1, 1999; 5(8): 2018 - 2024.
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L. Du Plessis, E. Dietzsch, M. Van Gele, N. Van Roy, P. Van Helden, M. I. Parker, D. K. Mugwanya, M. De Groot, M. P. Marx, M. J. Kotze, et al.
Mapping of Novel Regions of DNA Gain and Loss by Comparative Genomic Hybridization in Esophageal Carcinoma in the Black and Colored Populations of South Africa
Cancer Res., April 1, 1999; 59(8): 1877 - 1883.
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M.-T. Lin, R.-C. Lee, P.-C. Yang, F.-M. Ho, and M.-L. Kuo
Cyclooxygenase-2 Inducing Mcl-1-dependent Survival Mechanism in Human Lung Adenocarcinoma CL1.0 Cells. INVOLVEMENT OF PHOSPHATIDYLINOSITOL 3-KINASE/Akt PATHWAY
J. Biol. Chem., December 21, 2001; 276(52): 48997 - 49002.
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S. Murono, H. Inoue, T. Tanabe, I. Joab, T. Yoshizaki, M. Furukawa, and J. S. Pagano
Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells
PNAS, June 5, 2001; 98(12): 6905 - 6910.
[Abstract] [Full Text] [PDF]