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Furthermore, through a combination of proteomic profiling and functional in vitro studies with human osteoclasts and osteoblasts, we demonstrate that paracrine signaling from parental BC under β2-AR activation causes a robust decrease in human osteoclast differentiation and resorption activity, which is rescued in the presence of human osteoblasts. Conversely, metastatic bone tropic BC does not display this anti-osteoclastogenic effect. In conclusion, the observed changes in the proteomic profile of BC cells under β-AR activation that take place after metastatic dissemination, together with clinical data on epinephrine levels in BC patients, provided new insights on the sympathetic control of breast cancer and its implications on osteoclastic bone resorption.</jats:p>","journal":"Biomolecules","year":2023,"id":642286,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1670472,"name":"Daniela M. 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Nevertheless, the potential clinical benefits of exploiting β2-AR antagonists as a treatment for BC and bone loss-associated symptoms remain controversial. In this work, we show that, when compared to control individuals, the epinephrine levels in a cohort of BC patients are augmented in both earlier and late stages of the disease. Furthermore, through a combination of proteomic profiling and functional in vitro studies with human osteoclasts and osteoblasts, we demonstrate that paracrine signaling from parental BC under β2-AR activation causes a robust decrease in human osteoclast differentiation and resorption activity, which is rescued in the presence of human osteoblasts. Conversely, metastatic bone tropic BC does not display this anti-osteoclastogenic effect. In conclusion, the observed changes in the proteomic profile of BC cells under β-AR activation that take place after metastatic dissemination, together with clinical data on epinephrine levels in BC patients, provided new insights on the sympathetic control of breast cancer and its implications on osteoclastic bone resorption.</jats:p>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37189370","pmcid":"PMC10135909","openalex_id":"https://openalex.org/W4361274035","authors":[],"funders":[{"funder_name":"Fundo Europeu de Desenvolvimento Regional funds","grant_id":"POCI-01-0145-FEDER-030158","title":null},{"funder_name":"Fundo Europeu de Desenvolvimento Regional funds","grant_id":"PTDC/MED-PAT/30158/2017","title":"Pathological nerve sprouting in bone metastases: OSTEOCLASTS, what are you doing?"}],"total_grants":2,"fwci":1.0869,"citation_percentile":0.74894253,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2218-273X/13/4/622/pdf?version=1680262555","host_type":"journal"},{"url":"https://www.mdpi.com/2218-273X/13/4/622/pdf?version=1680262555","host_type":"publisher"},{"url":"https://www.mdpi.com/2218-273X/13/4/622/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/biom13040622","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37189370","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10135909","host_type":"repository"},{"url":"https://doaj.org/article/6eef239fb51b4bd98603fbf651098f5c","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/654cf9fe-cbfb-40fe-87ed-776b41029102","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10135909/pdf/biomolecules-13-00622.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10135909","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10135909?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/biom13040622","host_type":""},{"url":"https://dx.doi.org/10.3390/biom13040622","host_type":""},{"url":"http://www.scopus.com/inward/record.url?scp=85156105233&partnerID=8YFLogxK","host_type":""},{"url":"https://curis.ku.dk/ws/files/347003535/The_Secretome_of_Parental.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.3390/biom13040622","host_type":""}],"fields_of_study":["Cancer, Stress, Anesthesia, and Immune Response","Neuropeptides and Animal Physiology","Chemokine receptors and signaling","03 medical and health sciences","0302 clinical medicine","Humans","Female","Adrenergic Agents","Breast Neoplasms","Secretome","Proteomics","Bone Resorption","Epinephrine"],"mesh_terms":["Secretome","Bone Resorption","Breast Neoplasms","Epinephrine","Female","Humans","Adrenergic Agents","Proteomics"],"keywords":["Osteoclast","Breast cancer","Bone resorption","Medicine","Bone metastasis","Endocrinology","Internal medicine","Paracrine signalling","Cancer research","Cancer","Epinephrine","Metastatic breast cancer","Sympathetic nervous system","Receptor","Oncology","Proteomic","Beta-adrenergic","Proteomics","Breast Neoplasms","Microbiology","QR1-502","Article","Adrenergic Agents","Humans","Female","Secretome"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"cellosaurus"},{"name":"rrid"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T22:13:09.384726Z","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":[]}