PURPOSE: 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.
PURPOSE: 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: Leland W K Chung; Chia Ling Hsieh; Andrew Law; Shian Ying Sung; Thomas A Gardner; Masayuki Egawa; Shigeji Matsubara; Haiyen E Zhau Journal: Urology Date: 2003-11 Impact factor: 2.649
Authors: John M McAfee; Henry G Kattesh; Merlin D Lindemann; Brynn H Voy; Cheryl J Kojima; Nicole C Burdick Sanchez; Jeff A Carroll; Barbara E Gillespie; Arnold M Saxton Journal: J Anim Sci Date: 2019-11-04 Impact factor: 3.159