Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation

Andrew J. McKenzie, Stephanie R. Hicks, Kathryn V. Svec, Hannah Naughton, Zöe L. Edmunds, View ORCID ProfileAlan K. Howe
doi: https://doi.org/10.1101/238311
Andrew J. McKenzie
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie R. Hicks
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathryn V. Svec
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hannah Naughton
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zöe L. Edmunds
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan K. Howe
University of Vermont Larner College of Medicine Department of Pharmacology and the University of Vermont Cancer Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alan K. Howe
  • For correspondence: Alan.Howe@uvm.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

There is growing appreciation of the importance of the mechanical properties of the tumor microenvironment on disease progression. However, the role of extracellular matrix (ECM) stiffness and cellular mechanotransduction in epithelial ovarian cancer (EOC) is largely unknown. Here, we investigated the effect of substrate rigidity on various aspects of SKOV3 human EOC cell morphology and migration. Young’s modulus values of normal mouse peritoneum, a principal target tissue for EOC metastasis, were determined by atomic force microscopy (AFM) and hydrogels were fabricated to mimic these values. We find that cell spreading, focal adhesion formation, myosin light chain phosphorylation, and cellular traction forces all increase on stiffer matrices. Substrate rigidity also positively regulates random cell migration and, importantly, directional increases in matrix tension promote SKOV3 cell durotaxis. Matrix rigidity also promotes nuclear translocation of YAP1, an oncogenic transcription factor associated with aggressive metastatic EOC. Furthermore, disaggregation of multicellular EOC spheroids, a behavior associated with dissemination and metastasis, is enhanced by matrix stiffness through a mechanotransduction pathway involving ROCK, actomyosin contractility, and FAK. Finally, this pattern of mechanosensitivity is maintained in highly metastatic SKOV3ip.1 cells. These results establish that the mechanical properties of the tumor microenvironment may play a role in EOC metastasis.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted December 21, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation
Andrew J. McKenzie, Stephanie R. Hicks, Kathryn V. Svec, Hannah Naughton, Zöe L. Edmunds, Alan K. Howe
bioRxiv 238311; doi: https://doi.org/10.1101/238311
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation
Andrew J. McKenzie, Stephanie R. Hicks, Kathryn V. Svec, Hannah Naughton, Zöe L. Edmunds, Alan K. Howe
bioRxiv 238311; doi: https://doi.org/10.1101/238311

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2430)
  • Biochemistry (4791)
  • Bioengineering (3333)
  • Bioinformatics (14683)
  • Biophysics (6640)
  • Cancer Biology (5171)
  • Cell Biology (7429)
  • Clinical Trials (138)
  • Developmental Biology (4367)
  • Ecology (6874)
  • Epidemiology (2057)
  • Evolutionary Biology (9926)
  • Genetics (7346)
  • Genomics (9532)
  • Immunology (4557)
  • Microbiology (12686)
  • Molecular Biology (4948)
  • Neuroscience (28348)
  • Paleontology (199)
  • Pathology (809)
  • Pharmacology and Toxicology (1392)
  • Physiology (2024)
  • Plant Biology (4499)
  • Scientific Communication and Education (977)
  • Synthetic Biology (1299)
  • Systems Biology (3917)
  • Zoology (726)