Abstract
Chemerin [RARRES2 [retinoic acid receptor responder 2], TIG2 [tazarotene induced gene 2 (TIG2)]] is a multifunctional cytokine initially described in skin cultures upon exposure to the synthetic retinoid tazarotene. Its secreted pro-form, prochemerin, is widely expressed, found systemically, and is readily converted into active chemerin by various proteases. Subsequent studies elucidated major roles of chemerin as both a leukocyte chemoattractant as well as an adipokine. Chemerin's main chemotactic receptor, the G-protein coupled receptor CMKLR1, is expressed on macrophages, dendritic, and NK cells. With respect to its role in immunology, chemerin mediates trafficking of these cells to sites of inflammation along its concentration gradient, and likely helps coordinate early responses, as it has been shown to have antimicrobial and angiogenic properties, as well. Recently, there has been mounting evidence that chemerin is an important factor in various cancers. As with its role in immune responses—where it can act as both a pro- and anti-inflammatory mediator—the potential functions or correlations chemerin has in or with cancer appears to be context dependent. Most studies, however, suggest a downregulation or loss of chemerin/RARRES2 in malignancies compared to the normal tissue counterparts. Here, we perform a comprehensive review of the literature to date and summarize relevant findings in order to better define the roles of chemerin in the setting of the tumor microenvironment and tumor immune responses, with an ultimate focus on the potential for therapeutic intervention.
Highlights
Chemerin [ known as retinoic acid receptor responder 2 (RARRES2) or tazarotene induced gene 2 (TIG2)] is a multifunctional, chemoattractant protein known for its roles in adipogenesis, angiogenesis, skin function, metabolic activity, and, recently, tumorigenesis
Combined with previous reports that MMP-1 expression is associated with poor prognosis in esophageal cancer, the study suggested that chemerin could elicit pro-tumor effects in esophageal squamous cell carcinoma (ESCC) [107,108,109]
Transcriptional analysis of CCRL2 in Cutaneous Squamous Cell Carcinoma (CSCC) cell lines further revealed that CCRL2 expression was significantly increased on CSCC tumor cells in vitro, and enhanced tumor cell migration was observed as a result of increased levels of senescence-associated chemerin, which was abrogated by inhibition of chemerin in senescent fibroblasts
Summary
Chemerin [ known as retinoic acid receptor responder 2 (RARRES2) or tazarotene induced gene 2 (TIG2)] is a multifunctional, chemoattractant protein known for its roles in adipogenesis, angiogenesis, skin function, metabolic activity, and, recently, tumorigenesis. Elevated serum chemerin levels were observed in gastric cancer patients and were shown to be correlated with increased tumor invasiveness [29]. VEGF, IL-6, and MMP-7 have all been associated with enhanced tumor invasiveness in gastric cancer [68,69,70], while high expression of VEGF and IL-6 have been shown to stimulate metastasis of malignant cells and indicate poor clinical outcomes in gastric cancer patients, suggesting a potential impact of chemerin in this setting [69,70,71,72].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have