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

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...

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Main Authors: Raposo, T.P., Comes, Mireia Sueca, Idowu, Adeyemi, Agit, Bora, Hassall, James, Fadhil, Wakkas, Nica, Robert, Ecker, Rupert, Yao, Takashi, Ilyas, Mohammad
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Published: Elsevier 2018
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Online Access:https://eprints.nottingham.ac.uk/51365/
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author Raposo, T.P.
Comes, Mireia Sueca
Idowu, Adeyemi
Agit, Bora
Hassall, James
Fadhil, Wakkas
Nica, Robert
Ecker, Rupert
Yao, Takashi
Ilyas, Mohammad
author_facet Raposo, T.P.
Comes, Mireia Sueca
Idowu, Adeyemi
Agit, Bora
Hassall, James
Fadhil, Wakkas
Nica, Robert
Ecker, Rupert
Yao, Takashi
Ilyas, Mohammad
author_sort Raposo, T.P.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-513652024-08-15T15:31:10Z https://eprints.nottingham.ac.uk/51365/ 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 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. Elsevier 2018-06 Article PeerReviewed Raposo, T.P., Comes, Mireia Sueca, Idowu, Adeyemi, Agit, Bora, Hassall, James, Fadhil, Wakkas, Nica, Robert, Ecker, Rupert, Yao, Takashi and Ilyas, Mohammad (2018) CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer. Experimental and Molecular Pathology, 104 (3). pp. 190-198. ISSN 1096-0945 CD10; NEP; CALLA; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis https://www.sciencedirect.com/science/article/pii/S0014480017306500?via%3Dihub doi:10.1016/j.yexmp.2018.04.002 doi:10.1016/j.yexmp.2018.04.002
spellingShingle CD10; NEP; CALLA; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis
Raposo, T.P.
Comes, Mireia Sueca
Idowu, Adeyemi
Agit, Bora
Hassall, James
Fadhil, Wakkas
Nica, Robert
Ecker, Rupert
Yao, Takashi
Ilyas, Mohammad
CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title_full CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title_fullStr CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title_full_unstemmed CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title_short CD10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
title_sort cd10 inhibits cell motility but expression is associated with advanced stage disease in colorectal cancer
topic CD10; NEP; CALLA; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis
url https://eprints.nottingham.ac.uk/51365/
https://eprints.nottingham.ac.uk/51365/
https://eprints.nottingham.ac.uk/51365/