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An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours

Earlier studies identified the transmembrane cell surface C‐type lectin CLEC14A as a putative tumour endothelial marker. For CLEC14A to progress as a vascular target in solid tumours an in‐depth analysis of CLEC14A expression in human healthy and tumour tissue is needed. It is here shown that an ana...

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Autores principales: Robinson, Joseph, Whitworth, Katharine, Jinks, Elizabeth, Nagy, Zsuzsanna, Bicknell, Roy, Lee, Steven P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578301/
https://www.ncbi.nlm.nih.gov/pubmed/32696621
http://dx.doi.org/10.1002/cjp2.176
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author Robinson, Joseph
Whitworth, Katharine
Jinks, Elizabeth
Nagy, Zsuzsanna
Bicknell, Roy
Lee, Steven P
author_facet Robinson, Joseph
Whitworth, Katharine
Jinks, Elizabeth
Nagy, Zsuzsanna
Bicknell, Roy
Lee, Steven P
author_sort Robinson, Joseph
collection PubMed
description Earlier studies identified the transmembrane cell surface C‐type lectin CLEC14A as a putative tumour endothelial marker. For CLEC14A to progress as a vascular target in solid tumours an in‐depth analysis of CLEC14A expression in human healthy and tumour tissue is needed. It is here shown that an analysis of 5332 RNA expression profiles in the public domain confirmed high expression of CLEC14A in tumour compared to healthy human tissue. It is further shown by immunohistochemistry that CLEC14A protein is absent, or expressed at a very low level, in healthy human and primate tissue. In contrast, CLEC14A is expressed on the vasculature of a range of human solid tumours, with particularly high expression in more than half of renal cell carcinomas. Elevated levels of CLEC14A transcripts were identified in some non‐cancer pathologies; such comorbidities may need to be excluded from trials of therapies targeting this marker. It is further shown that, as CLEC14A expression can be induced by the absence of shear stress, it is imperative that freshly collected as opposed to aged or post‐mortem tissue be analysed. We conclude that CLEC14A is a promising target to enable development of novel anti‐cancer therapies for solid tumours.
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spelling pubmed-75783012020-10-23 An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours Robinson, Joseph Whitworth, Katharine Jinks, Elizabeth Nagy, Zsuzsanna Bicknell, Roy Lee, Steven P J Pathol Clin Res Original Articles Earlier studies identified the transmembrane cell surface C‐type lectin CLEC14A as a putative tumour endothelial marker. For CLEC14A to progress as a vascular target in solid tumours an in‐depth analysis of CLEC14A expression in human healthy and tumour tissue is needed. It is here shown that an analysis of 5332 RNA expression profiles in the public domain confirmed high expression of CLEC14A in tumour compared to healthy human tissue. It is further shown by immunohistochemistry that CLEC14A protein is absent, or expressed at a very low level, in healthy human and primate tissue. In contrast, CLEC14A is expressed on the vasculature of a range of human solid tumours, with particularly high expression in more than half of renal cell carcinomas. Elevated levels of CLEC14A transcripts were identified in some non‐cancer pathologies; such comorbidities may need to be excluded from trials of therapies targeting this marker. It is further shown that, as CLEC14A expression can be induced by the absence of shear stress, it is imperative that freshly collected as opposed to aged or post‐mortem tissue be analysed. We conclude that CLEC14A is a promising target to enable development of novel anti‐cancer therapies for solid tumours. John Wiley & Sons, Inc. 2020-07-21 /pmc/articles/PMC7578301/ /pubmed/32696621 http://dx.doi.org/10.1002/cjp2.176 Text en © 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Robinson, Joseph
Whitworth, Katharine
Jinks, Elizabeth
Nagy, Zsuzsanna
Bicknell, Roy
Lee, Steven P
An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title_full An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title_fullStr An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title_full_unstemmed An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title_short An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours
title_sort evaluation of the tumour endothelial marker clec14a as a therapeutic target in solid tumours
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578301/
https://www.ncbi.nlm.nih.gov/pubmed/32696621
http://dx.doi.org/10.1002/cjp2.176
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