CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer

Raposo, T.P.; Comes, Mireia Sueca; Idowu, Adeyemi; Agit, Bora; Hassall, James; Fadhil, Wakkas; Nica, Robert; Ecker, Rupert; Yao, Takashi; Ilyas, Mohammad

Abstract

Introduction
CD10 is a cell membrane-bound endopeptidase which is expressed in normal small bowel but not in normal colon. It is aberrantly expressed in a small proportion of colorectal cancers (CRC) and this has been associated with liver metastasis and poor prognosis. We sought to investigate the mechanism of CD10 activity and its association with clinicopathological features.

Material and methods
CD10 was stably knocked down by lentiviral shRNA transduction in the CRC cell lines SW480 and SW620 which are derived from a primary tumour and its corresponding metastasis respectively. Expression of epithelial – mesenchymal transition (EMT) markers was tested as well as the effect of knockdown on cell viability, migration and invasion assays. In addition, immunohistochemical expression of CD10 in primary colorectal tumours (N = 84) in a tissue microarray was digitally quantified and analysed for associations with clinicopathological variables.

Results
Knockdown of CD10 did not alter cell viability in SW480, but migration and invasion levels increased (P < 0.001 for each) and this was associated with a cadherin switch. In SW620, CD10 knockdown caused a reduction in cell viability after 72 h (P = 0.0018) but it had no effect on cell migration and invasion. Expression of epithelial CD10 in primary tumours was associated with presence of lymph node invasion (P = 0.001) and advanced Duke's stage (P = 0.001).

Conclusions
Our results suggest that the function of CD10 may change during tumour evolution. It may inhibit cell motility in early-stage disease whilst promoting cell viability in late-stage disease. It has a complex role and further studies are needed to elucidate the suitability of CD10 as a prognostic marker or therapeutic target.

Citation

Raposo, T., Comes, M. S., Idowu, A., Agit, B., Hassall, J., Fadhil, W., Nica, R., Ecker, R., Yao, T., & Ilyas, M. (2018). CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer. Experimental and Molecular Pathology, 104(3), https://doi.org/10.1016/j.yexmp.2018.04.002

• Journal Article Type: Article
• Acceptance Date: Apr 9, 2018
• Online Publication Date: Apr 11, 2018
• Publication Date: Jun 1, 2018
• Deposit Date: Apr 25, 2018
• Publicly Available Date: Apr 12, 2019
• Journal: Experimental and Molecular Pathology
• Print ISSN: 0014-4800
• Electronic ISSN: 1096-0945
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 104
• Issue: 3
• DOI: https://doi.org/10.1016/j.yexmp.2018.04.002
• Keywords: CD10; NEP; CALLA; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis
• Public URL: https://nottingham-repository.worktribe.com/output/961427
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0014480017306500?via%3Dihub
• Contract Date: Apr 25, 2018