Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins

Abstract

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.

The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation

“…1 Epithelial ovarian cancer metastasis is characterized by a spread of tumor cells within the peritoneal cavity and their subsequent invasion and proliferation within the organs of the pelvis. 4,5 These adhesion-related events are partly dependant on αv integrins, 6 specifically αvβ3, 7,8 which belongs to a family of cell surface integrin receptors.…”

The Ca2+ mobilisation and the inhibition of akt reduced the binding of PEO-1 cells to fibronectin

“…These results are consistent with previous findings. Carduner et al 19 reported that αv had an important role in ovarian cancer progression. Lessan et al 20 informed that β1 integrin may responsible for adhesion of ovarian cancer cells.…”

Review: Mechanotransduction in ovarian cancer: Shearing into the unknown

“…Additionally, ascites have been shown to enhance epithelial to mesenchymal transition (EMT) in ovarian cancer cells. 8,41,42 During EMT, a stationary epithelial cell transforms into a mesenchymal cell capable of motility. This transition is an important precursor for metastasis and chemoresistance.…”