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Expression of CCRL2 inhibits tumor growth by concentrating chemerin and inhibiting neoangiogenesis

ABSTRACT: CCRL2 is a non-signaling G protein-coupled receptor for chemerin, a leukocyte chemoattractant and an adipokine. Graft of B16 melanoma or Lewis lung carcinoma (LLC) cell lines in CCRL2 KO mice results in delayed growth of the tumors.

ORGANISM(S): Mus musculus

PROVIDER: GSE183914 | GEO | 2021/10/20

REPOSITORIES: GEO

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Chemerin inhibits cancer progression by impairing the maturation of neovessels

Project description:Chemerin is a leukocyte chemoattractant and an adipokine. Overexpression of chemerin by tumor cells or the host inhibits tumor progression in different mouse models, through a mechanism involving the chemerin receptor CMKLR1 and impairment of endothelial cell/pericyte interactions in neovessels.

2019-05-05 | GSE98672 | GEO

The role of chemerin in clear cell renal cell carcinoma

Project description:The most common subset of renal carcinoma, clear cell renal cell carcinoma (ccRCC), is characterized by accentuated accumulation of neutral lipids in lipid droplets and adipogenic trans-differentiation. Because obesity is a major risk factor in the development of ccRCC, we investigated the role of the adipokines in driving lipid metabolism and tumorigenesis in ccRCC. Through in silico screening, we identified the adipokine chemerin as candidate pro-oncogenic factor that is overexpressed in tumors and prognostic for patient outcome. Both ccRCC patient tumor tissues and serum exhibit elevated chemerin levels as compared to normal controls in an obesity-dependent manner. Attenuation of chemerin by several approaches in ccRCC cells led to significant impairments of tumor growth in both in vitro and in vivo models. A multi-omic approach revealed that chemerin suppresses fatty acid oxidation and maintains fatty acid levels which feed into transcriptional activation of hypoxia-inducible factor 2 (HIF2) expression. Suppression of chemerin therefore induced excess fatty acid oxidation and led to ferroptosis. CoQ and mitochondrial complex IV, derived mainly from lipid, were affected after chemerin inhibition, contributing to mitochondrial dysfunction and lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage, increased cell death, and diminished tumor growth, strengthening the translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology.

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Expression of CCRL2 inhibits tumor growth by concentrating chemerin and inhibiting neoangiogenesis

Project description:Expression of CCRL2 inhibits tumor growth by concentrating chemerin and inhibiting neoangiogenesis

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Adipokine chemerin impairs the receptive and metabolic functions of endometrial epithelial cells revealed by transcriptomic analysis

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CCRL2 expression by specialized lung capillary endothelial cells controls NK cells homing in lung cancer

Project description:Patterns of chemotactic receptors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represent a selective pathway for the homing of NK cells to the lung. CCRL2 is a non-signaling seven-transmembrane domain receptor able to control lung tumor growth. Total or endothelial cell targeted CCRL2 deletion or the deletion of its ligand chemerin were found to promote tumor progression in a KrasG12D/+;p53LoxP lung cancer model. This phenotype was dependent on the reduced recruitment of CD27-CD11b+ mature NK cells. Mining scRNA-seq databases identified CCRL2 expression as the hallmark of general alveolar lung capillary endothelial cells (gCaps). CCRL2 expression is epigenetically regulated in lung endothelium. In vivo administration of low doses of the demethylating agent 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells and lung protection in a tumor model. These results identify CCRL2 as a NK cell lung homing molecule that might be exploited to promote NK cell-mediated lung immune surveillance.

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2024-04-11 | E-MTAB-14016 | biostudies-arrayexpress

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Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions

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Transcription profiling of Mus musculus PBS vs IL-5 trerated LLC cells, and LLC vs B16 cells at baseline conditions

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The impact of chemerin on transcriptomic profile of swine luteal cells during mid-luteal phase of estrous cycle

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