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Actinic keratosis modelling in mice: A translational study

BACKGROUND: Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They a...

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Autores principales: Pillon, Arnaud, Gomes, Bruno, Vandenberghe, Isabelle, Cartron, Valérie, Cèbe, Patrick, Blanchet, Jean-Christophe, Sibaud, Vincent, Guilbaud, Nicolas, Audoly, Laurent, Lamant, Laurence, Kruczynski, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491107/
https://www.ncbi.nlm.nih.gov/pubmed/28662116
http://dx.doi.org/10.1371/journal.pone.0179991
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author Pillon, Arnaud
Gomes, Bruno
Vandenberghe, Isabelle
Cartron, Valérie
Cèbe, Patrick
Blanchet, Jean-Christophe
Sibaud, Vincent
Guilbaud, Nicolas
Audoly, Laurent
Lamant, Laurence
Kruczynski, Anna
author_facet Pillon, Arnaud
Gomes, Bruno
Vandenberghe, Isabelle
Cartron, Valérie
Cèbe, Patrick
Blanchet, Jean-Christophe
Sibaud, Vincent
Guilbaud, Nicolas
Audoly, Laurent
Lamant, Laurence
Kruczynski, Anna
author_sort Pillon, Arnaud
collection PubMed
description BACKGROUND: Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. OBJECTIVES: Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. METHODS: Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. RESULTS: An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC(®). CONCLUSION: These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease.
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spelling pubmed-54911072017-07-18 Actinic keratosis modelling in mice: A translational study Pillon, Arnaud Gomes, Bruno Vandenberghe, Isabelle Cartron, Valérie Cèbe, Patrick Blanchet, Jean-Christophe Sibaud, Vincent Guilbaud, Nicolas Audoly, Laurent Lamant, Laurence Kruczynski, Anna PLoS One Research Article BACKGROUND: Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist. Several treatments are available but their efficacy still needs to be improved. The UV-B-induced KA lesion mouse model is used in preclinical studies to assess the efficacy of novel molecules, even though it is often more representative of advanced AK or SCC. OBJECTIVES: Here we report on a translational study, comparing the various stages of AK development in humans and in the UV-B irradiated mouse model, as well as the optimization of photograph acquisition of AK lesions on mouse skin. METHODS: Human and mouse skin lesions were analysed by histology and immunohistochemistry. Mouse lesions were also assessed using a digital dermatoscope. RESULTS: An histological and phenotypic analysis, including p53, Ki67 and CD3 expression detection, performed on human and mouse AK lesions, shows that overall AK modelling in mice is relevant in the clinical situation. Some differences are observed, such as disorganization of keratinocytes of the basal layer and a number of atypical nuclei which are more numerous in human AK, whereas much more pronounced acanthosis is observed in skin lesion in mice. Thanks to this translational study, we are able to select appropriate experimental conditions for establishing either early or advanced stage AK or an SCC model. Furthermore, we optimized photograph acquisition of AK lesions on mouse skin by using a digital dermatoscope which is also used in clinics and allows reproducible photograph acquisition for further reliable assessment of mouse lesions. Use of this camera is illustrated through a pharmacological study assessing the activity of CARAC(®). CONCLUSION: These data demonstrate that this mouse model of UV-B-induced skin lesions is predictive for the identification of novel therapeutic treatments for both early and advanced stages of the disease. Public Library of Science 2017-06-29 /pmc/articles/PMC5491107/ /pubmed/28662116 http://dx.doi.org/10.1371/journal.pone.0179991 Text en © 2017 Pillon et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pillon, Arnaud
Gomes, Bruno
Vandenberghe, Isabelle
Cartron, Valérie
Cèbe, Patrick
Blanchet, Jean-Christophe
Sibaud, Vincent
Guilbaud, Nicolas
Audoly, Laurent
Lamant, Laurence
Kruczynski, Anna
Actinic keratosis modelling in mice: A translational study
title Actinic keratosis modelling in mice: A translational study
title_full Actinic keratosis modelling in mice: A translational study
title_fullStr Actinic keratosis modelling in mice: A translational study
title_full_unstemmed Actinic keratosis modelling in mice: A translational study
title_short Actinic keratosis modelling in mice: A translational study
title_sort actinic keratosis modelling in mice: a translational study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491107/
https://www.ncbi.nlm.nih.gov/pubmed/28662116
http://dx.doi.org/10.1371/journal.pone.0179991
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