Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

• Published in: British journal of cancer 2009-07, Vol.101 (1), p.106-115
• Main Authors: Charalambous, M P, Lightfoot, T, Speirs, V, Horgan, K, Gooderham, N J
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Molecular Diagnostics; Molecular Medicine; Oncology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605120

BACKGROUND: Cyclooxygenase-2 (COX-2) is selectively over-expressed in colorectal tumours. The mechanism of COX-2 induction in these tumours is not fully understood, although evidence suggests a possible link between nuclear factor (NF)- κ B and COX-2. We hypothesised an association between COX-2 expression and NF- κ B-p65, NF- κ B-p50 and I κ B-kinase- α (IKK α ) in both epithelial and stromal cells in human colorectal cancer. Methods: Using immunohistochemistry, we measured COX-2, NF- κ B-p65, NF- κ B-p65 nuclear localisation sequence (NLS), NF- κ B-p50, NF- κ B-p50 NLS and IKK α protein expression in matched colorectal biopsy samples comprising both non-tumour and adjacent tumour tissue from 32 patients with colorectal cancer. Results: We have shown that stromal cells of malignant and surrounding normal colorectal tissue express COX-2. In all cell types of malignant tissue, and in vascular endothelial cells (VECs) of neighbouring normal tissue, COX-2 expression was strongly associated with NF- κ B-p65 expression (Pearson's correlation, P =0.019 for macrophages, P =0.001 for VECs, P =0.002 for fibroblasts (malignant tissue), and P =0.011 for VECs (non-malignant tissue)) but not NF- κ B-p50 or IKK α . Conclusions: These data suggest that in these cells COX-2 induction may be mediated through activation of the canonical NF- κ B pathway. Finally, the lack of association between COX-2, NF- κ B-p65 or IKK α in stromal cells with the clinical severity of colorectal cancer as determined by Duke's stage, suggests that COX-2, NF- κ B-p65 and IKK α expression are possibly early post-initiation events, which could be involved in tumour progression.