Abstract

Chemerin is a multifunctional adipokine with established roles in inflammation, adipogenesis and glucose homeostasis. Increasing evidence suggest an important function of chemerin in cancer. Chemerin’s main cellular receptors, chemokine-like receptor 1 (CMKLR1), G-protein coupled receptor 1 (GPR1) and C-C chemokine receptor-like 2 (CCRL2) are expressed in most normal and tumor tissues. Chemerin’s role in cancer is considered controversial, since it is able to exert both anti-tumoral and tumor-promoting effects, which are mediated by different mechanisms like recruiting innate immune defenses or activation of endothelial angiogenesis. For this review article, original research articles on the role of chemerin and its receptors in cancer were considered, which are listed in the PubMed database. Additionally, we included meta-analyses of publicly accessible DNA microarray data to elucidate the association of expression of chemerin and its receptors in tumor tissues with patients’ survival.

Highlights

  • Chemerin—A Multifunctional Cytokine and AdipokineKnown as retinoic acid receptor responder 2 (RARRES2), is expressed ubiquitously, but is most abundant in adipose tissue and the liver

  • Chemerin, known as retinoic acid receptor responder 2 (RARRES2), is expressed ubiquitously, but is most abundant in adipose tissue and the liver

  • Whereas activation of chemokine-like receptor 1 (CMKLR1) leads to strong calcium mobilization and ERK1/2 phosphorylation, chemerin binding to G protein-coupled receptor 1 (GPR1) only leads to weak activation of both signaling mechanisms [4]

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Summary

Chemerin—A Multifunctional Cytokine and Adipokine

Known as retinoic acid receptor responder 2 (RARRES2), is expressed ubiquitously, but is most abundant in adipose tissue and the liver. The biologic activities of chemerin isoforms are primarily mediated by two receptors, chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor 1 (GPR1) [3]. Chemerin activation of CMKLR1 and GPR1 is not induced in parallel and short, inactive isoforms are elevated in the obese [9]. Chemerin protein levels are elevated in hypertensive patients, and experimental studies support a causative role of chemerin in the control of blood pressure [1]. Future work that evaluates the role of the short isoforms of chemerin will help to establish the function of this chemokine in blood pressure control. Similar to its role in inflammation, where chemerin acts as a proand anti-inflammatory factor, its effect in cancer depends on the disease context [16]

Chemerin and Leukocyte Recruitment
Intracellular Signaling of Chemerin Receptors
Expression of Chemerin and its Receptors and Cancer Survival
Hepatocellular Carcinoma
Findings
Conclusions

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