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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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/5000 |
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| author | Diana Al Delbany Virginie Robert Ingrid Dubois-Vedrenne Annalisa Del Prete Maxime Vernimmen Ayoub Radi Anne Lefort Frédérick Libert Valérie Wittamer Silvano Sozzani Marc Parmentier |
| author_facet | Diana Al Delbany Virginie Robert Ingrid Dubois-Vedrenne Annalisa Del Prete Maxime Vernimmen Ayoub Radi Anne Lefort Frédérick Libert Valérie Wittamer Silvano Sozzani Marc Parmentier |
| author_sort | Diana Al Delbany |
| collection | DOAJ |
| description | 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 <i>Ccrl2</i> 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 <i>Ccrl2</i> in tumor cells reversed the consequences of <i>Ccrl2</i> knockout in the host. The phenotypes associated with CCRL2 gain or loss of function were largely abrogated by knocking out the chemerin or <i>Cmklr1</i> 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. |
| first_indexed | 2024-03-10T07:04:49Z |
| format | Article |
| id | doaj.art-668128c52f0a4bd6a2f647e2b5bdd115 |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:04:49Z |
| publishDate | 2021-10-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-668128c52f0a4bd6a2f647e2b5bdd1152023-11-22T15:55:30ZengMDPI AGCancers2072-66942021-10-011319500010.3390/cancers13195000Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting NeoangiogenesisDiana Al Delbany0Virginie Robert1Ingrid Dubois-Vedrenne2Annalisa Del Prete3Maxime Vernimmen4Ayoub Radi5Anne Lefort6Frédérick Libert7Valérie Wittamer8Silvano Sozzani9Marc Parmentier10I.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumDepartment of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, ItalyI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, ItalyI.R.I.B.H.M and Welbio, Campus Erasme, Université Libre de Bruxelles, 808 Route de Lennik, B-1070 Brussels, BelgiumCCRL2 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 <i>Ccrl2</i> 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 <i>Ccrl2</i> in tumor cells reversed the consequences of <i>Ccrl2</i> knockout in the host. The phenotypes associated with CCRL2 gain or loss of function were largely abrogated by knocking out the chemerin or <i>Cmklr1</i> 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.https://www.mdpi.com/2072-6694/13/19/5000chemerinChemR23CMKLR1<i>Rarres2</i>tumor angiogenesis |
| spellingShingle | Diana Al Delbany Virginie Robert Ingrid Dubois-Vedrenne Annalisa Del Prete Maxime Vernimmen Ayoub Radi Anne Lefort Frédérick Libert Valérie Wittamer Silvano Sozzani Marc Parmentier Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis Cancers chemerin ChemR23 CMKLR1 <i>Rarres2</i> tumor angiogenesis |
| title | Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis |
| title_full | Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis |
| title_fullStr | Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis |
| title_full_unstemmed | Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis |
| title_short | Expression of CCRL2 Inhibits Tumor Growth by Concentrating Chemerin and Inhibiting Neoangiogenesis |
| title_sort | expression of ccrl2 inhibits tumor growth by concentrating chemerin and inhibiting neoangiogenesis |
| topic | chemerin ChemR23 CMKLR1 <i>Rarres2</i> tumor angiogenesis |
| url | https://www.mdpi.com/2072-6694/13/19/5000 |
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