The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis
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Ingrid Dubois-Vedrenne1,3, Diana Al Delbany1, Olivier De Henau1,4, Virginie Robert1,5, Maxime Vernimmen1, Francina Langa2, Anne Lefort1, Frédérick Libert1, Valérie Wittamer1 and Marc Parmentier1
1 I.R.I.B.H.M and Welbio, Université Libre de Bruxelles, Campus Erasme, B-1070 Brussels, Belgium
2 Centre d'Ingénierie Génétique Murine, Institut Pasteur, 75724 Paris, France
3 Present address: Institute for Medical Immunology, Université Libre de Bruxelles, 6041 Gosselies, Belgium
4 Present address: iTeos Therapeutics, 6041 Gosselies, Belgium
5 Present address: Ambiotis SAS, Canal Biotech 2, 31400 Toulouse, France
Keywords: chemerin; ChemR23; CMKLR1; Rarres2; tumor angiogenesis
Received: May 15, 2021 Accepted: August 13, 2021 Published: September 14, 2021
Chemerin, a multifunctional protein acting through the receptor ChemR23/CMKLR1, is downregulated in various human tumors and was shown to display antitumoral properties in mouse models of cancer. In the present study, we report that bioactive chemerin expression by tumor cells delays the growth of B16 melanoma and Lewis lung carcinoma in vivo. A similar delay is observed when chemerin is not expressed by tumor cells but by keratinocytes of the host mice. The protective effect of chemerin is mediated by CMKLR1 and appears unrelated to the recruitment of leukocyte populations. Rather, tumors grown in the presence of chemerin display a much smaller number of blood vessels, hypoxic regions early in their development, and larger necrotic areas. These observations likely explain the slower growth of the tumors. The anti-angiogenic effects of chemerin were confirmed in a bead sprouting assay using human umbilical vein endothelial cells. These results suggest that CMKLR1 agonists might constitute therapeutic molecules inhibiting the neoangiogenesis process in solid tumors.
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