Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis

CCRL2 belongs to the G protein-coupled receptor family and is one of the three chemerin receptors. It is considered as a non-signaling receptor, presenting chemerin to cells expressing the functional chemerin receptor ChemR23/CMKLR1 and possibly GPR1. In the present work, we investigate the role pla...

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Bibliographic Details
Published in:Cancers 2021-10, Vol.13 (19), p.5000
Main Authors: Al Delbany, Diana, Robert, Virginie, Dubois-Vedrenne, Ingrid, Del Prete, Annalisa, Vernimmen, Maxime, Radi, Ayoub, Lefort, Anne, Libert, Frédérick, Wittamer, Valérie, Sozzani, Silvano, Parmentier, Marc
Format: Article
Language:English
Subjects:
Angiogenesis
Animal models
Binding sites
Bioavailability
Biological activity
Breast cancer
Cancer
Carcinogenesis
Cell activation
Cell growth
Chemokine receptors
Chemokines
Cloning
CRISPR
Dendritic cells
Gastric cancer
Immune response
Inflammation
Melanoma
Metastasis
Mimicry
Neuroblastoma
Phenotypes
Prostate cancer
Protein turnover
Proteins
Signal transduction
Tumor cells
Tumorigenesis
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Summary:CCRL2 belongs to the G protein-coupled receptor family and is one of the three chemerin receptors. It is considered as a non-signaling receptor, presenting chemerin to cells expressing the functional chemerin receptor ChemR23/CMKLR1 and possibly GPR1. In the present work, we investigate the role played by CCRL2 in mouse cancer models. Loss of function of Ccrl2 accelerated the development of papillomas in a chemical model of skin carcinogenesis (DMBA/TPA), whereas the growth of B16 and LLC tumor cell grafts was delayed. Delayed tumor growth was also observed when B16 and LLC cells overexpress CCRL2, while knockout of Ccrl2 in tumor cells reversed the consequences of Ccrl2 knockout in the host. The phenotypes associated with CCRL2 gain or loss of function were largely abrogated by knocking out the chemerin or Cmklr1 genes. Cells harboring CCRL2 could concentrate bioactive chemerin and promote the activation of CMKLR1-expressing cells. A reduction of neoangiogenesis was observed in tumor grafts expressing CCRL2, mimicking the phenotype of chemerin-expressing tumors. This study demonstrates that CCRL2 shares functional similarities with the family of atypical chemokine receptors (ACKRs). Its expression by tumor cells can significantly tune the effects of the chemerin/CMKLR1 system and act as a negative regulator of tumorigenesis.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13195000