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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01253

Expression of bioactive chemerin by keratinocytes inhibits late stages of tumor development in a chemical model of skin carcinogenesis

 Ingrid Dubois-Vedrenne1, Olivier De Henau1, Virginie Robert1, Francina Langa2,  Diana Al Delbany1, Olivier Vosters1,  Edgar Angelats-Canals3,  Maxime Vernimmen1, Souphalone Luangsay1, 4,  Valérie Wittamer1 and  Marc Parmentier1, 5*
  • 1Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Belgium
  • 2Centre d'Ingéniérie Génétique Murine, Institut Pasteur, France
  • 3IRIBHM, Université libre de Bruxelles, Belgium
  • 4Ogeda SA, Belgium
  • 5Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Belgium

Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin1. 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.

Keywords: chemerin, CMKLR1, chemical carcinogenesis, Squamous cell carcinoma, ChemR23

Received: 18 Jul 2019; Accepted: 30 Oct 2019.

Copyright: © 2019 Dubois-Vedrenne, De Henau, Robert, Langa, Al Delbany, Vosters, Angelats-Canals, Vernimmen, Luangsay, Wittamer and Parmentier. 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.

* Correspondence: Mx. Marc Parmentier, Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Wavre, 1300, Belgium, mparment@ulb.ac.be