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.
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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)
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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
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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)
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