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Differential Expressions of Adhesive Molecules and Proteases Define Mechanisms of Ovarian Tumor Cell Matrix Penetration/Invasion

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
4
Identifiers
DOI: 10.1371/journal.pone.0018872
Keywords
  • Research Article
  • Biology
  • Molecular Cell Biology
  • Cellular Types
  • Stem Cells
  • Mesenchymal Stem Cells
  • Epithelial Cells
  • Extracellular Matrix
  • Medicine
  • Obstetrics And Gynecology
  • Gynecologic Cancers
  • Oncology
  • Basic Cancer Research
  • Metastasis
  • Tumor Physiology
  • Cancers And Neoplasms
  • Gynecological Tumors
  • Ovarian Cancer
Disciplines
  • Design
  • Medicine

Abstract

Epithelial ovarian cancer is an aggressive and deadly disease and understanding its invasion mechanisms is critical for its treatment. We sought to study the penetration/invasion of ovarian tumor cells into extracellular matrices (ECMs) using a fibroblast-derived three-dimensional (3D) culture model and time-lapse and confocal imaging. Twelve ovarian tumor cells were evaluated and classified into distinct groups based on their ECM remodeling phenotypes; those that degraded the ECM (represented by OVCAR5 cells) and those that did not (represented by OVCAR10 cells). Cells exhibiting a distinct ECM modifying behavior were also segregated by epithelial- or mesenchymal-like phenotypes and uPA or MMP-2/MMP-9 expression. The cells, which presented epithelial-like phenotypes, penetrated the ECM using proteases and maintained intact cell-cell interactions, while cells exhibiting mesenchymal phenotypes modified the matrices via Rho-associated serine/threonine kinase (ROCK) in the absence of apparent cell-cell interactions. Overall, this study demonstrates that different mechanisms of modifying matrices by ovarian tumor cells may reflect heterogeneity among tumors and emphasize the need to systematically assess these mechanisms to better design effective therapies.

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