Anti-RARRES2 monoclonal antibody, clone 483503 [Biotin]

Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and - independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally downregulated in multiple cancer types. Previous studies suggested that it can serve as an immune-dependent tumor suppressor by acting as a chemoattractant to recruit anticancer immune cells expressing its receptor, the chemerin chemokine receptor 1 (CMKLR1), to sites of tumor. In this study, we investigated the role of RARRES2 in adrenocortical carcinoma (ACC), a rare lethal malignancy in which aberrant Wnt/beta-catenin signaling is frequently detected. We show that RARRES2 expression is downregulated in ACC as compared with normal and benign adrenocortical tissues, which is a result of CpG hypermethylation. Despite minimal CMKLR1 expression and lack of phenotypic tumor-suppressive effect with exogenous RARRES2 treatment, RARRES2 overexpression in ACC cell lines not only reduced cell proliferation, cell invasion and tumorigenicity in vitro, but also inhibited tumor growth in vivo in two immunodeficient mouse xenograft models. Mechanistically, RARRES2 overexpression in ACC cells inhibited Wnt/beta-catenin pathway activity by promoting beta-catenin phosphorylation and degradation, it also inhibited the phosphorylation of p38 mitogen-activated protein kinase. Thus our study identifies RARRES2 as a novel tumor suppressor for ACC, which can function through an immune-independent mechanism.

Background: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. Results: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. Conclusions: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.