You are here

  • Home
  • Archive
  • Volume 24, Issue 2
  • Interactions of Human Peritoneal Mesothelial Cells With Serous Ovarian Cancer Cell Spheroids—Evidence for a Mechanical and Paracrine Barrier Function of the Peritoneal Mesothelium

Article Text

Article menu
Download PDFPDF
Basic Science
Interactions of Human Peritoneal Mesothelial Cells With Serous Ovarian Cancer Cell Spheroids—Evidence for a Mechanical and Paracrine Barrier Function of the Peritoneal Mesothelium
  1. Sylvia Stadlmann, MD*,
  2. Hans Feichtinger, MD†,
  3. Gregor Mikuz, MD†,
  4. Christian Marth, MD‡,
  5. Alain Gustave Zeimet, MD‡,
  6. Manfred Herold, MD§,
  7. Cornelius Knabbe, MD∥ and
  8. Felix Albert Offner, MD
  1. *Institute of Pathology, Kantonsspital Baden AG, Baden, Switzerland; Departments of
  2. †Pathology,
  3. ‡Gynecology and Obstetrics, and
  4. §Internal Medicine, Innsbruck Medical University, Innsbruck, Austria;
  5. ∥Department of Clinical Chemistry, Robert Bosch Hospital, Stuttgart, Germany; and
  6. Institute of Pathology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
  1. Address correspondence and reprint requests to Felix Albert Offner, MD, Institute of Pathology, Academic Teaching Hospital Feldkirch, Carinagasse 47, A-6800 Feldkirch, Austria. E-mail: felix.offner{at}lkhf.at.

Abstract

Background Ovarian carcinoma spreads by implantation of tumor cells onto the peritoneal mesothelium. We established a 3-dimensional coculture model to simulate the interactions of ovarian carcinoma cell aggregates with human peritoneal mesothelial cells (HPMC).

Methods Multicellular tumor spheroids (MCTS) of the human ovarian cancer cell line SK-OV-3 were directly inoculated onto either confluent HPMC monolayers or their submesothelial matrix or were cocultured with mesothelium without direct cellular contact.

Results and Discussions Inoculation of MCTS onto submesothelial matrix resulted in rapid attachment (within 30 minutes) of the tumor cell aggregates followed by rapid dissemination (within 12 hours) and growth of tumor cells. Intact mesothelium increased the time required for MCTS attachment (up to 180 minutes) and led to almost complete inhibition of tumor cell dissemination and to 47% tumor growth suppression. Bromodeoxyuridine incorporation into tumor cell nuclei was almost completely abolished in cocultured MCTS. Growth also was inhibited in MCTS treated with supernatants of HPMC. Analysis of coculture supernatants revealed that HPMC-derived transforming growth factor β (TGF-β) was almost completely bound by MCTS. Addition of a function-blocking anti–TGF-β antibody (30 μg/mL) to the cocultures abrogated the growth inhibitory effect of the mesothelium by 50%.

Conclusions The present model provides a dynamic system to study the complex interactions of ovarian carcinoma cells with HPMC over extended periods and suggests that the mesothelium constitutes a mechanical and partly TGF-β–mediated paracrine barrier to the progression of ovarian cancer.

  • Mesothelial cells
  • Ovarian carcinoma
  • Transforming growth factor β
  • TGF-β
  • Tumor spheroids

https://doi.org/10.1097/IGC.0000000000000036

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Footnotes

    • The authors declare no conflicts of interest.