Anna-Maria Stock1, Franziska Klee1, Karolina Edlund2, Marianna Grinberg3, Seddik Hammad4, Rosemarie Marchan2, Cristina Cadenas2, Bernd Niggemann1, Kurt S Zänker1, Jörg Rahnenführer3, Marcus Schmidt5, Jan G Hengstler6, Frank Entschladen1. 1. Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany. 2. Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany. 3. Department of Statistics, TU Dortmund University, Dortmund, Germany. 4. Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany Department of Forensic Medicine and Veterinary Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt. 5. Department of Obstetrics and Gynecology, University Hospital, Mainz, Germany. 6. Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany hengstler@ifado.de.
Abstract
BACKGROUND: Tumor cell migration is a prerequisite for metastasis formation. The role of the actin-modulating protein, gelsolin, in metastasis is controversial, as previous studies have reported associations with both worse and better prognosis. MATERIALS AND METHODS: We analysed the association of gelsolin mRNA levels with metastasis-free survival in three cohorts (n=766) of patients with node-negative breast cancer. To determine its effect on migration, gelsolin expression was down-regulated as well as overexpressed in breast cancer cell lines. RESULTS: Higher gelsolin expression correlated with lower tumor stage and grade, and slower cell proliferation, and was associated with longer metastasis-free survival (hazard ratio (HR)=0.60, p<0.001) in patients with estrogen receptor-positive (ER(+)) erb-b2 receptor tyrosine kinase 2-negative (HER2(-)) tumors. Conversely, the opposite association was observed in those with ER(-)HER(-) tumors (HR=1.95, p=0.014). Down-regulation of gelsolin using siRNA in MCF-7 and MDA-MB-468 cells increased cell migration, whereas overexpression had the opposite effect. CONCLUSION: High gelsolin levels are associated with better prognosis in ER(+)HER2(-) breast cancer and a reduction in tumor cell migration. Copyright
BACKGROUND:Tumor cell migration is a prerequisite for metastasis formation. The role of the actin-modulating protein, gelsolin, in metastasis is controversial, as previous studies have reported associations with both worse and better prognosis. MATERIALS AND METHODS: We analysed the association of gelsolin mRNA levels with metastasis-free survival in three cohorts (n=766) of patients with node-negative breast cancer. To determine its effect on migration, gelsolin expression was down-regulated as well as overexpressed in breast cancer cell lines. RESULTS: Higher gelsolin expression correlated with lower tumor stage and grade, and slower cell proliferation, and was associated with longer metastasis-free survival (hazard ratio (HR)=0.60, p<0.001) in patients with estrogen receptor-positive (ER(+)) erb-b2 receptor tyrosine kinase 2-negative (HER2(-)) tumors. Conversely, the opposite association was observed in those with ER(-)HER(-) tumors (HR=1.95, p=0.014). Down-regulation of gelsolin using siRNA in MCF-7 and MDA-MB-468 cells increased cell migration, whereas overexpression had the opposite effect. CONCLUSION: High gelsolin levels are associated with better prognosis in ER(+)HER2(-) breast cancer and a reduction in tumor cell migration. Copyright
Authors: Christoph B Messner; Vadim Demichev; Daniel Wendisch; Laura Michalick; Matthew White; Anja Freiwald; Kathrin Textoris-Taube; Spyros I Vernardis; Anna-Sophia Egger; Marco Kreidl; Daniela Ludwig; Christiane Kilian; Federica Agostini; Aleksej Zelezniak; Charlotte Thibeault; Moritz Pfeiffer; Stefan Hippenstiel; Andreas Hocke; Christof von Kalle; Archie Campbell; Caroline Hayward; David J Porteous; Riccardo E Marioni; Claudia Langenberg; Kathryn S Lilley; Wolfgang M Kuebler; Michael Mülleder; Christian Drosten; Norbert Suttorp; Martin Witzenrath; Florian Kurth; Leif Erik Sander; Markus Ralser Journal: Cell Syst Date: 2020-06-02 Impact factor: 10.304