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[Cancer Research 59, 198-204, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 198-204, January 1, 1999]
© 1999 American Association for Cancer Research

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 nonsteroidal anti-inflammatory drugs reduce the risk of esophageal carcinoma, we studied the expression of cyclooxygenase-2 (COX-2) in esophageal squamous cell carcinomas (SCCs; n = 172) and in esophageal adenocarcinomas (ADCs; n = 27). Using immunohistochemistry, we observed COX-2 expression in 91% of the SCCs and in 78% of the ADCs. Western blot analysis showed enhanced expression of the COX-2 protein in some tumors as compared with normal esophageal squamous epithelium, whereas similar amounts of the COX-1 protein were found in normal and cancerous tissues. COX expression was also studied in two esophageal cancer cell lines (OSC-1 and OSC-2) to evaluate the functional relevance of COX-2-derived prostaglandins (PGs). OSC-2 cells expressed COX-2 but not COX-1, whereas OSC-1 cells expressed high levels of COX-1 but showed only a very weak COX-2 expression. Accordingly, PGE2 synthesis was 600 times higher in the OSC-2 cells as compared with the OSC-1 cells. Treatment of OSC-2 cells with the selective COX-2 inhibitors flosulide and NS-398 concentration dependently suppressed PGE2 synthesis and proliferation and also induced apoptosis. In contrast, no effect of the COX-2 inhibitors was seen in OSC-1 cells. Our data demonstrate that COX-2 is expressed in the majority of esophageal SCCs and ADCs and that COX-2-derived PGs play an important role in the regulation of proliferation and apoptosis of esophageal tumor cells. It is concluded that inhibition of COX-2 may be useful in the therapy of esophageal cancer.




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K. J. Sales, A. A. Katz, M. Davis, S. Hinz, R. P. Soeters, M. D. Hofmeyr, R. P. Millar, and H. N. Jabbour
Cyclooxygenase-2 Expression and Prostaglandin E2 Synthesis Are Up-Regulated in Carcinomas of the Cervix: A Possible Autocrine/Paracrine Regulation of Neoplastic Cell Function via EP2/EP4 Receptors
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2243 - 2249.
[Abstract]