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Coexpression of Cyclooxygenases (COX-1, COX-2) and Vascular Endothelial Growth Factors (VEGF-A, VEGF-C) in Esophageal Adenocarcinoma

¹ Department of Surgery and ² Institute for Pathology and Pathologic Anatomy, Technical University of Munich, Munich, Germany

Requests for reprints: Burkhard H.A. von Rahden, Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr 22, D-81677 Munich, Germany. Phone: 49-894-140-4165; Fax: 49-894-140-4865; E-mail: vrahden{at}nt1.chir.med.tu-muenchen.de.

Cyclooxygenases (COX), especially COX-2, are considered to be involved in carcinogenesis. Our study was initiated to test whether expression of COX isoforms (COX-1 and COX-2) is linked to expression of potent inducers of angiogenesis [vascular endothelial growth factor (VEGF)-A] and lymphangiogenesis (VEGF-C) in esophageal adenocarcinoma. One hundred twenty-three esophageal adenocarcinomas were investigated by means of quantitative reverse transcription-PCR for expression of COX-1, COX-2, VEGF-A, and VEGF-C. Additionally, COX-2 protein expression was determined using immunohistochemistry. Three esophageal cancer cell lines (OE-33, OSC-1, and OSC-2) were treated with COX-inhibiting substances (diclofenac, rofecoxib, and SC-560) and the effect on expression of the four genes was determined. COX-2 protein expression was found in all carcinomas under analysis. RNA expression levels of COX-1 and COX-2 varied markedly in carcinoma tissues and correlated significantly with each other (P < 0.001, r = 0.726). Furthermore, COX expression correlated with expression of VEGF-A (COX-1: P < 0.001, r = 0.753; COX-2: P < 0.001, r = 0.764) and VEGF-C (COX-1: P < 0.001, r = 0.778; COX-2: P < 0.001; r = 0.613). Exposure of esophageal cancer cell lines OE-33, OSC-1, and OSC-2 with three COX-inhibiting substances (diclofenac, rofecoxib, and SC-560) resulted in significantly reduced expression of VEGF-A and VEGF-C. In conclusion, our data suggest that both COX isoforms may be involved in the pathogenesis of esophageal adenocarcinoma, as they are linked to the expression of important modulators of angiogenesis (VEGF-A) and lymphangiogenesis (VEGF-C).

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