{"doi":"10.17615/1255-yf95","title":"C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1","abstract":"C-C Chemokine receptor five knockout (Ccr5-/-) mice develop fewer experimental pulmonary metastases than wild type (WT) mice. This phenomenon was explored by applying gene-expression profiling to the lungs of mice with these metastases. Consequently, Erythroid Differentiation Regulator 1 (Erdr1) was identified as upregulated in the WT mice. Though commonly associated with bone marrow stroma, Erdr1 was differentially expressed in WT pulmonary mesenchymal cells (PMCs) and murine embryonic fibroblasts (MEFs). Moreover, the Ccr5 ligand Ccl4 increased its expression by 3.36 ± 0.14 fold. Ccr5 signaling was dependent on the Map2k but not the Pi3k pathway since treatment with U0126 inhibited upregulation of Erdr1 but treatment with LY294002 increased the expression by 3.44 ± 0.92 fold (p < 0.05). Erdr1's effect on B16-F10 melanoma metastasis was verified by the adoptive transfer of WT MEFs into Ccr5-/- mice. In this model, MEFs that had been transduced with Erdr1 shRNA lowered metastasis by 33% compared to control transduced MEFs. The relevance of ERDR1 on human disease was assessed by co-culturing chronic lymphocytic leukemia (CLL) cells with M2-10B4 stromal cells that had been transfected with shRNA or control plasmids. After 96 hours of co-culture, the cell counts were higher with control cell lines compared with Erdr1 knockdown lines (OR 1.88 ± 0.27, 2.52 ± 0.66 respectively). This increase was associated with a decrease in apoptotic cells (OR 0.69 ± 0.18, 0.58 ± 0.12 respectively).","journal":"UNC Libraries","year":2020,"id":140593,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":605408,"name":"Robert L. Mango","orcid":null,"position":1,"is_corresponding":false},{"id":598603,"name":"Michelle L. West","orcid":"0000-0003-1080-8452","position":2,"is_corresponding":false},{"id":262408,"name":"Jonathan S. Serody","orcid":"0000-0003-4568-1092","position":3,"is_corresponding":false},{"id":598048,"name":"E.C. McCook","orcid":null,"position":4,"is_corresponding":false},{"id":598049,"name":"Hendrik W. van Deventer","orcid":null,"position":5,"is_corresponding":false},{"id":605407,"name":"Qing Ping Wu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:17.077903Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}