Actin Cytoskeleton Participation in the Onset of IL-1 beta Induction of an Invasive Mesenchymal-like Phenotype in Epithelial MCF-7 Cells

作者：Franco Barraza Janusz; Valdivia Silva Julio E; Zamudio Meza Horacio; Castillo Aida; Garcia Zepeda Eduardo A; Benitez Bribiesca Luis; Meza Isaura^*

来源：Archives of Medical Research, 2010, 41(3): 170-181.

DOI：10.1016/j.arcmed.2010.04.010

• IL-1 beta
• Breast cancer cells
• Actin cytoskeleton
• Phenotype transition

Background. Interleukin 1 beta (IL-1 beta) 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-1 beta-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-1 beta and specific inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP activity and expression of S100A4 in cells treated with IL-1 beta were assessed by migration assays, zymograms and immunoblots.
Results. Exposure to IL-1 beta 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-1 beta-stimulated cells expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and MMP-2 and invasion of extracellular matrix proteins.
Conclusions. IL-1 beta 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.

• 出版日期2010-4