Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Research Article

Co-evolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse

Triantafyllos Stylianopoulos, John D Martin, Matija Snuderl, Fotios Mpekris, Saloni R Jain and Rakesh K. Jain
Triantafyllos Stylianopoulos
Department of Mechanical and Manufacturing Engineering, University of Cyprus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: tstylian@ucy.ac.cy
John D Martin
Edwin L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matija Snuderl
Pathology, Massachusetts General Hospital and Harvard Medical School
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fotios Mpekris
Department of Mechanical and Manufacturing Engineering, University of Cyprus
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saloni R Jain
Radiation Oncology, Massachusetts General Hospital and Harvard Medical School
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rakesh K. Jain
Edwin L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/0008-5472.CAN-12-4521
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid pressure is the isotropic stress exerted by the fluid phase. We recently demonstrated that growth-induced solid stress is on the order of 1.3-13.0 kPa (10-100 mmHg) - high enough to cause compression of fragile blood vessels resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress and fluid pressure. First, we performed in vivo experiments and found that growth-induced stress is related to tumor volume through a bi-exponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared to the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histological sections of human cancers that demonstrate such vessel deformations. Finally, we found that fluid pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular pressure. Crucially, fluid pressure does not cause vessel compression of tumor vessels. Major Findings. Growth-induced solid stress is accumulated in tumors during growth. Growth-induced and externally applied solid stresses are additive and might affect cancer cell growth in two ways: directly by compressing cancer cells and indirectly by deforming blood vessels and thus, reducing delivery of nutrients.

  • Received December 11, 2012.
  • Revision received April 23, 2013.
  • Accepted April 24, 2013.
  • Copyright © 2013, American Association for Cancer Research.
Next
Back to top

Published OnlineFirst May 10, 2013
doi: 10.1158/0008-5472.CAN-12-4521

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Co-evolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Co-evolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse
Triantafyllos Stylianopoulos, John D Martin, Matija Snuderl, Fotios Mpekris, Saloni R Jain and Rakesh K. Jain
Cancer Res May 10 2013 DOI: 10.1158/0008-5472.CAN-12-4521

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Co-evolution of solid stress and interstitial fluid pressure in tumors during progression: Implications for vascular collapse
Triantafyllos Stylianopoulos, John D Martin, Matija Snuderl, Fotios Mpekris, Saloni R Jain and Rakesh K. Jain
Cancer Res May 10 2013 DOI: 10.1158/0008-5472.CAN-12-4521
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • USP6NL fuels aerobic glycolysis in breast cancer
  • NFATc1 promotes anti-tumoral T cell functions in NSCLC
  • Oncogene transformation promotes missing-self NK recognition
Show more Research Article
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement