title: PPAR-gamma is expressed and NF-kB pathway is activated and correlates positively with COX-2 expression in stromal myofibroblasts surrounding colon adenocarcinomas.
abstract: OBJECTIVE
  Accumulated evidence indicates that carcinogenesis is closely associated with the transformation of normal stroma into a 'reactive' stromal phenotype. The present study investigated the role of PPARgamma, COX-2 and p-IkB-alpha--important molecular targets of colon cancer chemoprevention--in this stromal remodeling by evaluating and comparing the expression of these factors in stromal myofibroblasts, macrophages and endothelial cells that surround normal colonic mucosa and colon cancer.
  
  
  METHODS
  Immunohistochemical methodology was employed on archived paraffin-embedded sections prepared from tumors and adjacent normal colon from 45 patients with colon adenocarcinomas. Double immunostaining with the universal marker for myofibroblasts (alpha-smooth muscle actin/alpha-SMA) as second primary antibody was also performed.
  
  
  RESULTS
  Stromal macrophages and endothelial cells expressed these factors both in normal colonic mucosa and colon cancer. By contrast, stromal myofibroblasts expressed PPARgamma, COX-2 and p-IkB-alpha only in colon adenocarcinomas (77.7%, 100% and 100% of cases, respectively) and not in normal colon. COX-2 and p-IkB-alpha expressions were strongly correlated in these cells (P < 0.001). PPARgamma, COX-2 and p-IkB-alpha expression did not correlate with the stage or differentiation of the adenocarcinomas.
  
  
  CONCLUSIONS
  NF-kB pathway is activated and COX-2 expression is upregulated in stromal myofibroblasts surrounding colon adenocarcinomas compared to normal colon. Induction of COX-2 expression is primarily induced by NF-kB. NSAIDs, selective COX-2 inhibitors and PPARgamma ligands may exert their chemoprophylactic properties through direct actions on these cells.
authors.affiliation: Department of Anatomy and Histology-Embryology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Gerasimos P
authors.initials: GP
authors.lastname: Vandoros
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Konstantinopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Sotiropoulou-Bonikou
authors.forename: Athina
authors.initials: A
authors.lastname: Kominea
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Papachristou
authors.forename: Michalis V
authors.initials: MV
authors.lastname: Karamouzis
authors.forename: Maria
authors.initials: M
authors.lastname: Gkermpesi
authors.forename: Ioannis
authors.initials: I
authors.lastname: Varakis
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D032342:Muscle Cells / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000032:analysis*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D016328:NF-kappa B; D047495:PPAR gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human