Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins
| Autor: | Franck Carreiras, Johanne Leroy-Dudal, Olivier Gallet, Ludovic Carduner, Cédric R. Picot, Sabrina Kellouche |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Cell Vimentin Biology Carcinoma Ovarian Epithelial medicine Biomarkers Tumor Humans Epithelial–mesenchymal transition Neoplasms Glandular and Epithelial Cell Proliferation Ovarian Neoplasms Tumor microenvironment Cell growth Mesenchymal stem cell Ascites General Medicine Integrin alphaV medicine.disease Matrix Metalloproteinases medicine.anatomical_structure Oncology Cell culture Cancer research biology.protein Female Ovarian cancer |
| Zdroj: | Clinicalexperimental metastasis. 31(6) |
| ISSN: | 1573-7276 |
| Popis: | At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence. The presence of ascites, which acts as a dynamic reservoir of active molecules and cellular components, correlates with the OC peritoneal metastasis and is associated with poor prognosis. Since epithelial-mesenchymal transition (EMT) is involved in different phases of OC progression, we have investigated the effect of the unique ascitic tumor microenvironment on the EMT status and the behavior of OC cells. The exposure of three OC cell lines to ascites leads to changes in cellular morphologies. Within ascites, OC cells harboring an initial intermediate epithelial phenotype are characterized by marked dislocation of epithelial markers (E-cadherin, ZO-1 staining) while OC cells initially harboring an intermediate mesenchymal phenotype strengthen their mesenchymal markers (N-cadherin, vimentin). Ascites differentially triggers a dissemination phenotype related to the initial cell features by either allowing the proliferation and the formation of spheroids and the extension of colonies for cells that present an initial epithelial intermediate phenotype, or favoring the migration of cells with a mesenchymal intermediate phenotype. In an ascitic microenvironment, a redeployment of αv integrins into cells was observed and the ascites-induced accentuation of the two different invasive phenotypes (i.e. spheroids formation or migration) was shown to involve αv integrins. Thus, ascites induces a shift toward an unstable intermediate state of the epithelial-mesenchymal spectrum and confers a more aggressive cell behavior that takes on a different pathway based on the initial epithelial-mesenchymal cell features. |
| Databáze: | OpenAIRE |
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