Actin cytoskeleton participation in the onset of IL-1beta induction of an invasive mesenchymal-like phenotype in epithelial MCF-7 cells.

Abstract

BACKGROUND:

Interleukin 1 beta (IL-1beta) and other inflammatory cytokines are reported to induce phenotypic changes in epithelial breast cancer tumor cells related to increased invasiveness. Mechanisms involved in the process are not well understood.

METHODS:

The noninvasive breast cancer epithelial cell line MCF-7 was used to investigate the IL-1beta-induced phenotype. Live cells expressing EGFP-actin were monitored for cell morphology changes and actin cytoskeleton dynamics by time-lapse video microscopy in the presence of IL-1beta and specific inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP activity and expression of S100A4 in cells treated with IL-1beta were assessed by migration assays, zymograms and immunoblots.

RESULTS:

Exposure to IL-1beta specifically induced a change in MCF-7 cells from a typical epithelial morphology into elongated cells, showing numerous dynamic actin-rich lamellae and peripheral ruffles characteristic of fibroblasts. These cells could scatter from compact cell colonies and respond to chemoattractants such as the homing-associated chemokine CXCL-12. Pharmacological blockage of actin signaling pathways and negative mutants of RhoGTPases revealed that actin reorganization and enhanced motility are regulated via PI3K/Rac 1 activation. IL-1beta-stimulated cells expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and MMP-2 and invasion of extracellular matrix proteins.

CONCLUSIONS:

IL-1beta induces a PI3K/Rac 1-regulated reorganization of the actin cytoskeleton of MCF-7 cells that is required for cell scattering, elongation and migration. The enhanced motility is accompanied by expression of protein markers correlated with invasive behavior.

• Authors: Janusz Franco-Barraza, Julio E Valdivia-Silva, Horacio Zamudio-Meza, Aida Castillo, Eduardo A García-Zepeda, Luis Benítez-Bribiesca, Isaura Meza
• Journal: Archives of medical research (Arch Med Res) Vol. 41 Issue 3 Pg. 170-81 (Apr 2010) ISSN: 1873-5487 [Electronic] United States
• PMID: 20682174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 IMSS. Published by Elsevier Inc. All rights reserved.

Chemical References

• Actins
• CXCR4 protein, human
• IL1R1 protein, human
• Interleukin-1beta
• RAC1 protein, human
• Receptors, CXCR4
• Receptors, Interleukin-1 Type I
• Recombinant Proteins
• Phosphatidylinositol 3-Kinases
• rac1 GTP-Binding Protein

Topics

• Actins (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Shape (drug effects)
• Cytoskeleton (drug effects, metabolism)
• Epithelial Cells (drug effects, metabolism, pathology)
• Female
• Humans
• Interleukin-1beta (metabolism, pharmacology)
• Mesoderm (drug effects, metabolism, pathology)
• Microscopy, Video
• Neoplasm Invasiveness (pathology)
• Phenotype
• Phosphatidylinositol 3-Kinases (metabolism)
• Receptors, CXCR4 (metabolism)
• Receptors, Interleukin-1 Type I (metabolism)
• Recombinant Proteins (pharmacology)
• Signal Transduction
• rac1 GTP-Binding Protein (metabolism)