Article type: Research Article
Authors: Konstantinopoulos, Panagiotis A.; ; | Vandoros, Gerasimos P.; | Karamouzis, Michalis V.; | Gkermpesi, Maria | Sotiropoulou-Bonikou, Georgia | Papavassiliou, Athanasios G.;
Affiliations: Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece | Division of Hematology–Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA | Department of Pathology, Aeghion General Hospital, Aeghion, Greece | Division of Hematology–Oncology, University of Pittsburgh, Pittsburgh, PA, USA | Department of Anatomy and Histology–Embryology, School of Medicine, University of Patras, Patras, Greece
Note: [] P.A. Konstantinopoulos and G.P. Vandoros contributed equally to this work.
Note: [] Corresponding author: Prof. Athanasios G. Papavassiliou, Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, GR-11527 Athens, Greece. Tel.: +30 210 7462509; Fax: +30 210 7791207; E-mail: papavas@med.uoa.gr
Abstract: Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κB transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κB, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-IκB-α (phosphorylated IκB-α), EGF-R, COX-2, NF-κB and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-IκB-α, NF-κB, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-IκB-α, NF-κB, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κB transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.
Keywords: Colon adenocarcinoma, stromal myofibroblasts, EGF-R, AP-1, NF-κB, COX-2, VEGF
Journal: Analytical Cellular Pathology, vol. 29, no. 6, pp. 477-482, 2007
