TY - JOUR

T1 - Combined activity of COX-1 and COX-2 is increased in non-neoplastic colonic mucosa from colorectal neoplasia patients

AU - Jensen, Thorbjørn Søren Rønn

AU - Mahmood, Badar

AU - Damm, Morten Bach

AU - Backe, Marie Balslev

AU - Dahllöf, Mattias Salling

AU - Poulsen, Steen Seier

AU - Hansen, Mark Berner

AU - Bindslev, Niels

PY - 2018/2/27

Y1 - 2018/2/27

N2 - Background: Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. Methods: Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). Results: Combined COX-1 and COX-2 activity was higher in CRN-pts, p=0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. Conclusions: In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

AB - Background: Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. Methods: Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). Results: Combined COX-1 and COX-2 activity was higher in CRN-pts, p=0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. Conclusions: In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

KW - Biopsy

KW - Carcinogenesis

KW - Cyclooxygenase

KW - Endoscopic

KW - Short circuit current (SCC)

KW - Tuft cells

UR - http://www.scopus.com/inward/record.url?scp=85042566407&partnerID=8YFLogxK

U2 - 10.1186/s12876-018-0759-1

DO - 10.1186/s12876-018-0759-1

M3 - Journal article

C2 - 29486731

AN - SCOPUS:85042566407

VL - 18

JO - B M C Gastroenterology

JF - B M C Gastroenterology

SN - 1471-230X

IS - 1

M1 - 31

ER -