Construction and characteristics of an E-cadherin-related three-dimensional suspension growth model of ovarian cancer

Sci Rep. 2014 Jul 10;4:5646. doi: 10.1038/srep05646.

Abstract

Ovarian cancer is the deadliest of all gynecologic malignancies. Metastatic ovarian cancer cells exist mainly in the form of multi-cellular spheroids (MCSs) in the ascites of patients with advanced ovarian cancer. We hypothesized that E-cadherin, as an important cell-adhesion molecule, might play an important role in the formation and survival of MCSs. Therefore, we established a three-dimensional suspension culture model of ovarian cancer cells that express high levels of E-cadherin to investigate their growth, proliferation, and resistance to chemotherapeutic drugs by CCK-8 assays. Compared to the cell suspension masses formed by cells with low or absent E-cadherin expression, the MCSs of high E-cadherin SKOV-3 cells had larger volumes, tighter cellular connections, and longer survival times. Although the suspension cell masses of all three cell lines were proliferatively stagnant, possibly due to cell cycle arrest at G1/S, cell mortality at 72 h after cisplatin treatment was significantly decreased in the high E-cadherin SKOV-3 cells compared to SKOV-3 cells without E-cadherin expression and to OVCAR-3 cells with low E-cadherin expression. We conclude, therefore, E-cadherin plays a vital role in MCS formation, maintenance, and drug resistance in ovarian cancer and could be a potential target for late-stage ovarian cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / metabolism
  • Cell Culture Techniques
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / physiology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cisplatin / pharmacology
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • G1 Phase Cell Cycle Checkpoints / physiology
  • Humans
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology

Substances

  • Cadherins
  • Cell Adhesion Molecules
  • Cisplatin