Expression of Cox-2 in human breast cancer cells as a critical determinant of epithelial-to-mesenchymal transition and invasiveness. (February 2014)

• Record Type: Journal Article
• Authors: Bocca, Claudia; Ievolella, Monica; Autelli, Riccardo; Motta, Manuela; Mosso, Luciano; Torchio, Bruno; Bozzo, Francesca; Cannito, Stefania; Paternostro, Claudia; Colombatto, Sebastiano; Parola, Maurizio; Miglietta, Antonella
• Is Part Of: Expert opinion on therapeutic targets. Volume 18:Number 2(2014:Feb.)
• Page Start: 121
• Page End: 135
• Publication Date: 2014-02
• Subjects: Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1517/14728222.2014.860447
• Languages: English
• ISSNs: 1744-7631

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Cyclooxygenase-2 (COX-2) is overexpressed in several malignancies and is implicated in breast cancer progression.</p> <p> <bold> <italic>Objectives:</italic> </bold> We investigated whether changes in COX-2 expression may affect epithelial-to-mesenchymal transition (EMT) and then invasive potential of human breast cancer cells, in relationship with hypoxia. COX-2-null MCF-7 human breast cancer cells, MCF-7 cells transiently expressing COX-2 and COX-2-expressing MDA-MB-231 cells were employed.</p> <p> <bold> <italic>Results:</italic> </bold> COX-2 overexpression resulted in downregulation of E-cadherin and β-catenin, upregulation of vimentin, N-cadherin and SNAI1, suggesting EMT occurrence. COX-2-overexpressing MCF-7 cells were also characterized by increased invasiveness and release of matrix-metalloproteinase-9. The above-mentioned characteristics, homologous to those detected in highly invasive MDA-MB-231 cells, were reverted by treatment of COX-2-overexpressing MCF-7 cells with celecoxib, a COX-2-specific inhibitor, partly through the inhibition of COX-2-related intracellular generation of reactive oxygen species. Hypoxia further exacerbated COX-2 expression, EMT changes and invasive ability in both COX-2-overexpressing MCF-7 cells and MDA-MB-231 cells. Finally, immunohistochemistry performed on samples from normal and neoplastic human breast tissues revealed that COX-2-positive malignant cells were also positive for EMT-related antigens, hypoxia-inducible factor (HIF)-2α and the oxidative stress marker heme oxygenase.</p> <p> <bold> <italic>Conclusions:</italic> </bold> These findings support the existence of a direct link between COX-2 overexpression, EMT and invasiveness in human breast cancer cells, emphasizing the role of hypoxic microenvironment.</p> </abstract>