Localisation of a Novel Cathepsin L Isoform in Colorectal Cancer

• Published in: Endoscopy
• Main Authors: Sullivan, S, O'Sullivan, J, Coss, A, Tosetto, M, Wang, L, O'Donoghue, D, Hyland, J, Fennelly, D, Sheahan, K, Mulcahy, H
• Format: Conference Proceeding
• Language: English
• Published: 18.12.2006
• ISSN: 0013-726X; 1438-8812
• DOI: 10.1055/s-2006-956783

Category: Colorectal Background: Cathepsin L is a lysosomal cysteine protease which functions in degrading proteins. Its cellular localisation and functional role in colorectal cancer progression is unknown. Nuclear localisation of Cathespin L has not been documented in colorectal cancer. Design: Using immunohistochemistry and tissue microarrays, we investigated the localisation (cytoplasmic and nuclear), percentage positivity and intensity levels of Cathepsin L in 182 colorectal tumours. For 44/182 cases, normal non-adjacent mucosa was also examined. Results were correlated with pathological data. Using cell fractionation and western blot analyses, the molecular weight of the cytoplasmic and nuclear cathespin L isoforms were determined. Results: Significant associations were detected between epithelial nuclear and cytoplasmic Cathepsin L intensity against Dukes staging (p=0.008 and p=0.006 respectively). Epithelial cytoplasmic intensity correlated with vascular invasion (p=0.03). Both epithelial and stromal (nuclear and cytoplasmic) intensities were significantly higher in tumours versus normal non-adjacent mucosa (all p values ≤0.002). The molecular weight of the pro- and active form of the nuclear and cytoplasmic Cathespin L were identical. Conclusions: The presence of nuclear Cathepsin L may play a role in disease progression, activate gene expression and be involved in proteolytic processing of specific nuclear proteins.