Patient-derived and artificial ascites have minor effects on MeT-5A mesothelial cells and do not facilitate ovarian cancer cell adhesion.

Manuela Estermann,Yen-Lin Huang,Alke Petri-Fink,Barbara Rothen-Rutishauser,Dedy Septiadi,Ching-Yeu Liang,Viola Heinzelmann-Schwarz,Francis Jacob,Barbara Drasler,Danilo Ritz,Shama Ahmad

doi:10.1371/journal.pone.0241500

Abstract

The presence of ascites in the peritoneal cavity leads to morphological and functional changes of the peritoneal mesothelial cell layer. Cells loose cell-cell interactions, rearrange their cytoskeleton, activate the production of fibronectin, and change their cell surface morphology in a proinflammatory environment. Moreover, ovarian cancer cell adhesion has been shown to be facilitated by these changes due to increased integrin- and CD44-mediated binding sites. In this study, the biological responsiveness of the human pleural mesothelial cell line MeT-5A to patient-derived and artificial ascites was studied in vitro and adhesion of ovarian cancer cells, i.e. SKOV-3 cells, investigated. Changes were mainly observed in cells exposed to artificial ascites containing higher cytokine concentrations than patient-derived ascites. Interestingly, reduced cell-cell interactions were already observed in untreated MeT-5A cells and effects on tight junction protein expression and permeability upon exposure to ascites were minor. Ascites induced upregulation of CDC42 effector protein 2 expression, which affects stress fiber formation, however significant F-actin reorganization was not observed. Moreover, fibronectin production remained unchanged. Analysis of mesothelial cell surface characteristics showed upregulated expression of intercellular adhesion molecule 1, slightly increased hyaluronic acid secretion and decreased microvillus expression upon exposure to ascites. Nevertheless, the observed changes were not sufficient to facilitate adhesion of SKOV-3 cells on MeT-5A cell layer. This study revealed that MeT-5A cells show a reduced biological responsiveness to the presence of ascites, in contrast to published studies on primary human peritoneal mesothelial cells.

Highlights

Ovarian cancer is usually diagnosed at an advanced stage with metastases in the peritoneum and omentum resulting in low survival rates [1,2,3]
The TNF-α, IL-1β, IL-6, and TGF-β1 concentrations in patient-derived ascites were evaluated, as these cytokines were shown to be key factors in inducing structural and functional alterations in mesothelial cells [15]. The secretion of these cytokines (TNF-α, IL-6, and TGF-β) weaken the host antitumor immunity and allow the cancer cells to escape the immune system, which has been activated through the proinflammatory process of cancer progression and metastasis [36]
peritoneal cancer (PeC), which displays greater involvement in extraovarian sites with microscopically tumor-free ovaries, showed slightly higher TNF-α, similar IL-1β, and significantly increased IL-6 and TGF-β1 concentrations when compared to OvC3 and OvC4 (Table 1)

Summary

Introduction

Ovarian cancer is usually diagnosed at an advanced stage with metastases in the peritoneum and omentum resulting in low survival rates [1,2,3]. Minor effects of ascites on MeT-5A mesothelial cells. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion