Dataset Information

EPO does not promote interaction between the erythropoietin and beta-common receptors.

ABSTRACT: A direct interaction between the erythropoietin (EPOR) and the beta-common (?c) receptors to form an Innate Repair Receptor (IRR) is controversial. On one hand, studies have shown a functional link between EPOR and ?c receptor in tissue protection while others have shown no involvement of the ?c receptor in tissue repair. To date there is no biophysical evidence to confirm a direct association of the two receptors either in vitro or in vivo. We investigated the existence of an interaction between the extracellular regions of EPOR and the ?c receptor in silico and in vitro (either in the presence or absence of EPO or EPO-derived peptide ARA290). Although a possible interaction between EPOR and ?c was suggested by our computational and genomic studies, our in vitro biophysical analysis demonstrates that the extracellular regions of the two receptors do not specifically associate. We also explored the involvement of the ?c receptor gene (Csf2rb) under anaemic stress conditions and found no requirement for the ?c receptor in mice. In light of these studies, we conclude that the extracellular regions of the EPOR and the ?c receptor do not directly interact and that the IRR is not involved in anaemic stress.

SUBMITTER: Cheung Tung Shing KS

PROVIDER: S-EPMC6102255 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

EPO does not promote interaction between the erythropoietin and beta-common receptors.

Cheung Tung Shing Karen S KS Broughton Sophie E SE Nero Tracy L TL Gillinder Kevin K Ilsley Melissa D MD Ramshaw Hayley H Lopez Angel F AF Griffin Michael D W MDW Parker Michael W MW Perkins Andrew C AC Dhagat Urmi U

Scientific reports 20180820 1

A direct interaction between the erythropoietin (EPOR) and the beta-common (βc) receptors to form an Innate Repair Receptor (IRR) is controversial. On one hand, studies have shown a functional link between EPOR and βc receptor in tissue protection while others have shown no involvement of the βc receptor in tissue repair. To date there is no biophysical evidence to confirm a direct association of the two receptors either in vitro or in vivo. We investigated the existence of an interaction betwee ...[more]

PMID: 30127368

Similar Datasets

Project description:BackgroundMultiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated.MethodsMyeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study. Transcript levels were analysed by quantitative PCR and cell surface levels of EPOR in primary cells by flow cytometry. Knockdown of EPOR by short interfering RNA was used to show specific EPOR signaling in the myeloma cell line INA-6. Flow cytometry was used to assess viability in primary cells treated with EPO in the presence and absence of neutralizing anti-EPOR antibodies. Gene expression data for total therapy 2 (TT2), total therapy 3A (TT3A) trials and APEX 039 and 040 were retrieved from NIH GEO omnibus and EBI ArrayExpress.ResultsWe show that the EPOR is expressed in myeloma cell lines and in primary myeloma cells both at the mRNA and protein level. Exposure to recombinant human EPO (rhEPO) reduced viability of INA-6 myeloma cell line and of primary myeloma cells. This effect could be partially reversed by neutralizing antibodies against EPOR. In INA-6 cells and primary myeloma cells, janus kinase 2 (JAK-2) and extracellular signal regulated kinase 1 and 2 (ERK-1/2) were phosphorylated by rhEPO treatment. Knockdown of EPOR expression in INA-6 cells reduced rhEPO-induced phospo-JAK-2 and phospho-ERK-1/2. Co-cultures of primary myeloma cells with bone marrow-derived stroma cells did not protect the myeloma cells from rhEPO-induced cell death. In four different clinical trials, survival data linked to gene expression analysis indicated that high levels of EPOR mRNA were associated with better survival.ConclusionsOur results demonstrate for the first time active EPOR signaling in malignant plasma cells. EPO-mediated EPOR signaling reduced the viability of myeloma cell lines and of malignant primary plasma cells in vitro. Our results encourage further studies to investigate the importance of EPO/EPOR in multiple myeloma progression and treatment.Trial registration[Trial registration number for Total Therapy (TT) 2: NCT00083551 and TT3: NCT00081939 ].

Dataset Information

EPO does not promote interaction between the erythropoietin and beta-common receptors.

Publications

EPO does not promote interaction between the erythropoietin and beta-common receptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets