title: Gelsolin Is Associated with Longer Metastasis-free Survival and Reduced Cell Migration in Estrogen Receptor-positive Breast Cancer.
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.
  
  
  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.
  
  
  CONCLUSIONS
  High gelsolin levels are associated with better prognosis in ER(+)HER2(-) breast cancer and a reduction in tumor cell migration.
authors.affiliation: Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Stock
authors.affiliation: Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Klee
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Grinberg
authors.affiliation: 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.
authors.forename: Seddik
authors.initials: S
authors.lastname: Hammad
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Marchan
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cadenas
authors.affiliation: Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.affiliation: Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany.
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zänker
authors.affiliation: Department of Statistics, TU Dortmund University, Dortmund, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany hengstler@ifado.de.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Institute of Immunology and Experimental Oncology, Center for Biomedical Education and Research, Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051345:Destrin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C495824:DSTN protein, human; D051345:Destrin; D011960:Receptors, Estrogen
keywords: Gelsolin; breast cancer; cytoskeleton; estrogen receptor-positive; migration; prognosis