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Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis

Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin(1). Its expression is frequently downregulated in human tumors, including in melanoma and squamous cell carcinoma of the skin and anti-tumoral properties of chemerin were reported in mo...

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Autores principales: Dubois-Vedrenne, Ingrid, De Henau, Olivier, Robert, Virginie, Langa, Francina, Javary, Joaquim, Al Delbany, Diana, Vosters, Olivier, Angelats-Canals, Edgar, Vernimmen, Maxime, Luangsay, Souphalone, Wittamer, Valérie, Parmentier, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873210/
https://www.ncbi.nlm.nih.gov/pubmed/31803622
http://dx.doi.org/10.3389/fonc.2019.01253
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author Dubois-Vedrenne, Ingrid
De Henau, Olivier
Robert, Virginie
Langa, Francina
Javary, Joaquim
Al Delbany, Diana
Vosters, Olivier
Angelats-Canals, Edgar
Vernimmen, Maxime
Luangsay, Souphalone
Wittamer, Valérie
Parmentier, Marc
author_facet Dubois-Vedrenne, Ingrid
De Henau, Olivier
Robert, Virginie
Langa, Francina
Javary, Joaquim
Al Delbany, Diana
Vosters, Olivier
Angelats-Canals, Edgar
Vernimmen, Maxime
Luangsay, Souphalone
Wittamer, Valérie
Parmentier, Marc
author_sort Dubois-Vedrenne, Ingrid
collection PubMed
description Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin(1). Its expression is frequently downregulated in human tumors, including in melanoma and squamous cell carcinoma of the skin and anti-tumoral properties of chemerin were reported in mouse tumor graft models. In the present study, we report the development of spontaneous skin tumors in aged ChemR23-deficient mice. In order to test the potential therapeutic benefit of chemerin analogs, a transgenic model in which bioactive chemerin is over-expressed by basal keratinocytes was generated. These animals are characterized by increased levels of chemerin immunoreactivity and bioactivity in the skin and the circulation. In a chemical carcinogenesis model, papillomas developed later, were less numerous, and their progression to carcinomas was delayed. Temporal control of chemerin expression by doxycycline allowed to attribute its effects to late stages of carcinogenesis. The protective effects of chemerin were partly abrogated by ChemR23 invalidation. These results demonstrate that chemerin is able to delay very significantly tumor progression in a model that recapitulates closely the evolution of solid cancer types in human and suggest that the chemerin-ChemR23 system might constitute an interesting target for therapeutic intervention in the cancer field.
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spelling pubmed-68732102019-12-04 Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis Dubois-Vedrenne, Ingrid De Henau, Olivier Robert, Virginie Langa, Francina Javary, Joaquim Al Delbany, Diana Vosters, Olivier Angelats-Canals, Edgar Vernimmen, Maxime Luangsay, Souphalone Wittamer, Valérie Parmentier, Marc Front Oncol Oncology Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin(1). Its expression is frequently downregulated in human tumors, including in melanoma and squamous cell carcinoma of the skin and anti-tumoral properties of chemerin were reported in mouse tumor graft models. In the present study, we report the development of spontaneous skin tumors in aged ChemR23-deficient mice. In order to test the potential therapeutic benefit of chemerin analogs, a transgenic model in which bioactive chemerin is over-expressed by basal keratinocytes was generated. These animals are characterized by increased levels of chemerin immunoreactivity and bioactivity in the skin and the circulation. In a chemical carcinogenesis model, papillomas developed later, were less numerous, and their progression to carcinomas was delayed. Temporal control of chemerin expression by doxycycline allowed to attribute its effects to late stages of carcinogenesis. The protective effects of chemerin were partly abrogated by ChemR23 invalidation. These results demonstrate that chemerin is able to delay very significantly tumor progression in a model that recapitulates closely the evolution of solid cancer types in human and suggest that the chemerin-ChemR23 system might constitute an interesting target for therapeutic intervention in the cancer field. Frontiers Media S.A. 2019-11-15 /pmc/articles/PMC6873210/ /pubmed/31803622 http://dx.doi.org/10.3389/fonc.2019.01253 Text en Copyright © 2019 Dubois-Vedrenne, De Henau, Robert, Langa, Javary, Al Delbany, Vosters, Angelats-Canals, Vernimmen, Luangsay, Wittamer and Parmentier. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Dubois-Vedrenne, Ingrid
De Henau, Olivier
Robert, Virginie
Langa, Francina
Javary, Joaquim
Al Delbany, Diana
Vosters, Olivier
Angelats-Canals, Edgar
Vernimmen, Maxime
Luangsay, Souphalone
Wittamer, Valérie
Parmentier, Marc
Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title_full Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title_fullStr Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title_full_unstemmed Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title_short Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis
title_sort expression of bioactive chemerin by keratinocytes inhibits late stages of tumor development in a chemical model of skin carcinogenesis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873210/
https://www.ncbi.nlm.nih.gov/pubmed/31803622
http://dx.doi.org/10.3389/fonc.2019.01253
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