Abstract
BackgroundCyclooxygenase (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.MethodsBiopsies 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).ResultsCombined 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.ConclusionsIn 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.
Highlights
Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN)
body mass index (BMI) and age was higher in Colorectal neoplasia patients (CRN-pts) compared to ctrls with BMI displaying statistically significance (BMI: CRN-pts 27.2 (±1.2) vs ctrls 23.2 (±1.2), p = 0.048
Using Real time polymerase chain reaction (RT-qPCR), we examined the expression of COX-1 and COX-2 in colonic mucosa from CRN-pts and ctrls
Summary
Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). 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. Observation and documentation of possible altered signaling in pre-neoplastic colorectal mucosa from humans are essentials for future development of targeted pharmacotherapy against CRC and colorectal neoplasia (CRN). The mechanism behind NSAIDs’s chemoprevention is most likely due to inhibition of cyclooxygenase (COX) enzymes, other mechanisms of aspirins CRN-prevention are possible [6]. PGE2 has been demonstrated to promote proliferation, cell migration, angiogenesis and reduce
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