title: TNFα-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells.
abstract: OBJECTIVE
  Up to now it has been unclear whether stromal/epithelial interaction affects progression of colon cancer. This study was designed to examine effects of tumour necrosis factor alpha (TNFα)-activated stromal cyclooxygenase-2 (COX-2) signalling on proliferation and invasiveness of colon cancer epithelial cells.
  
  
  METHODS
  Cyclooxygenase-2 mRNA and protein were determined by real-time PCR and western blotting and prostaglandin E2 (PGE2 ) was assayed by radioimmunoassay. Cell proliferation and invasiveness were determined by transwell chamber assays and protein kinase C (PKC) was assayed by Biotrak(™) PKC Assay System.
  
  
  RESULTS
  Our results indicated that TNFα, a powerful inflammatory cytokine, strongly promoted COX-2 expression and PGE2 production in colon cancer-associated fibroblasts. Using in vitro assays for estimating proliferative and invasive potential, we discovered that activation of stromal COX-2 signalling significantly promoted proliferation and invasiveness of colon cancer epithelial cells. In addition, selective COX-2 inhibitor N-[2-(Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide, blocked such proliferative and invasive effects on the cancer epithelial cells. In this process, PKC was involved in activation of COX-2 signalling in the fibroblasts.
  
  
  CONCLUSIONS
  We conclude that activation of stromal COX-2 signalling by TNFα played a major role in promoting proliferation and invasiveness of colon cancer epithelial cells.
authors.affiliation: Arizona Cancer Center, The University of Arizona, Tucson, AZ, 85724, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: P
authors.initials: P
authors.lastname: Lance
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011493:Protein Kinase C; D015232:Dinoprostone