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

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)-kappa B and COX-2. We hypothesised an association between COX-2 expression and NF-kappa B-p65, NF-kappa B-p50 and I kappa B-kinase-alpha (IKK alpha) in both epithelial and stromal cells in human colorectal cancer. METHODS: Using immunohistochemistry, we measured COX-2, NF-kappa B-p65, NF-kappa B-p65 nuclear localisation sequence (NLS), NF-kappa B-p50, NF-kappa B-p50 NLS and IKK alpha 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-kB-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-kappa B-p50 or IKK alpha. CONCLUSIONS: These data suggest that in these cells COX-2 induction may be mediated through activation of the canonical NF-kappa B pathway. Finally, the lack of association between COX-2, NF-kappa B-p65 or IKK alpha in stromal cells with the clinical severity of colorectal cancer as determined by Duke's stage, suggests that COX-2, NF-kappa B-p65 and IKK alpha expression are possibly early post-initiation events, which could be involved in tumour progression. British Journal of Cancer ( 2009) 101, 106-115. doi: 10.1038/sj.bjc.6605120 www.bjcancer.com Published online 9 June 2009 (C) 2009 Cancer Research UK