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.

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.

• Authors: Anna-Maria Stock, Franziska Klee, Karolina Edlund, Marianna Grinberg, Seddik Hammad, Rosemarie Marchan, Cristina Cadenas, Bernd Niggemann, Kurt S Zänker, Jörg Rahnenführer, Marcus Schmidt, Jan G Hengstler, Frank Entschladen
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 10 Pg. 5277-85 (Oct 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26408687 (Publication Type: Journal Article)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• DSTN protein, human
• Destrin
• Receptors, Estrogen

Topics

• Breast Neoplasms (genetics, mortality, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Destrin (genetics, metabolism)
• Female
• Humans
• MCF-7 Cells
• Neoplasm Grading
• Neoplasm Staging
• Receptors, Estrogen (metabolism)
• Survival Analysis