The Secretome of Parental and Bone Metastatic Breast Cancer Elicits Distinct Effects in Human Osteoclast Activity after Activation of β2 Adrenergic Signaling
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The sympathetic nervous system (SNS), particularly through the β2 adrenergic receptor (β2-AR), has been linked with breast cancer (BC) and the development of metastatic BC, specifically in the bone. 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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 622 |
| Tidsskrift | Biomolecules |
| Vol/bind | 13 |
| Udgave nummer | 4 |
| Antal sider | 25 |
| ISSN | 2218-273X |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The authors are grateful to the patients that kindly provided the plasma samples and to the staff of the Breast Cancer Clinic and Laboratory Medicine Department of the Portuguese Oncology Institute of Porto (IPOPorto) for their contribution to the samples’ collection. The mass spectrometry-based proteomics approach was performed by Hugo Osório at the i3S Proteomics Scientific Platform. This work had support from the Portuguese Mass Spectrometry Network, integrated into the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening, member of the PT-OPENSCREEN (NORTE-01-0145-FEDER-085468) and PPBI (PPBI-POCI-01-0145-FEDER-022122). The authors acknowledge the support of the i3S Scientific Platform Bioimaging, a member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122), for confocal imaging acquisition.
Funding Information:
This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and Portuguese funds through FCT/MCTES in the framework of the project “SproutOC” (POCI-01-0145-FEDER-030158, PTDC/MED-PAT/30158/2017). F.C. is a recipient of the Ph.D. fellowship SFRH/BD/128771/2017. M.C. is a recipient of the Ph.D. fellowship 2020.05177.BD. D.M.S. is a recipient of post-doctoral fellowship SFRH/BPD/115341/2016.
Publisher Copyright:
© 2023 by the authors.
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