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

AACR logo

  • Register
  • Log in
  • Log out
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • Log out
  • My Cart

Search

  • Advanced search
Cancer Research
Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Articles

Inhibition of Tumor Invasion of Smooth Muscle Cell Layers by Recombinant Human Metalloproteinase Inhibitor

Yves A. DeClerck, Tsuey-Dawn Yean, Darkin Chan, Hiroyuki Shimada and Keith E. Langley
Yves A. DeClerck
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tsuey-Dawn Yean
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Darkin Chan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Shimada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith E. Langley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published April 1991
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

Matrix metalloproteinases secreted by tumor cells play an important role in the proteolytic degradation of the extracellular matrix during invasion. In a previous study, we showed that the degradation of extracellular matrices by human HT 1080 fibrosarcoma cells is suppressed by endothelial cells. The identification of inhibitors of metalloproteinases secreted by endothelial cells led us to postulate that these inhibitors were responsible for the suppressive effect (Cancer Res., 46: 3580–3586, 1986).

In the present study, we have investigated the inhibitory activity of one of these inhibitors designated metalloproteinase inhibitor (MI)/tissue inhibitor of metalloproteinases (TIMP)-2 on the degradation and invasion of rat smooth muscle cell matrices by two invasive tumor cell lines, the c-Ha-ras-1 transfected rat embryo cell line 4R and the HT 1080 human fibrosarcoma cell line. The inhibitor was obtained in recombinant form from the culture medium of Chinese hamster ovary cells transfected with a human MI complementary DNA.

Recombinant MI/TIMP-2 inhibited several matrix metalloproteinases identified in the culture medium of the tumor cell lines including interstitial collagenase, Mr 72,000 gelatinase (type IV collagenase), and Mr 92,000 gelatinase. Approximately 70% inhibition of the degradation of smooth muscle cell matrices was observed when the recombinant inhibitor was present along with cultured cells at a concentration of 10 µg/ml. Similarly, inhibition of the penetration of a multilayer of growing smooth muscle cells and their surrounding matrix was demonstrated. The inhibitor had no effect on cell growth or attachment.

Thus, recombinant MI/TIMP-2, like TIMP, is a potent inhibitor of tumor invasion. Since both inhibitors are secreted by endothelial cells (J. Biol. Chem., 264: 17445–17453, 1989), they may play an important role in protecting large blood vessels from invasion.

Footnotes

  • ↵1 This work was supported by Grant CA 42919 from the NIH, Department of Health and Human Services, to Y. A. D., and by a research agreement between Childrens Hospital of Los Angeles and Amgen, Inc.

  • ↵2 To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027.

  • Received September 6, 1990.
  • Accepted January 31, 1991.
  • ©1991 American Association for Cancer Research.
PreviousNext
Back to top
April 1991
Volume 51, Issue 8
  • Table of Contents
  • Table of Contents (PDF)
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)

Sign up for alerts

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.
Inhibition of Tumor Invasion of Smooth Muscle Cell Layers by Recombinant Human Metalloproteinase Inhibitor
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Inhibition of Tumor Invasion of Smooth Muscle Cell Layers by Recombinant Human Metalloproteinase Inhibitor
Yves A. DeClerck, Tsuey-Dawn Yean, Darkin Chan, Hiroyuki Shimada and Keith E. Langley
Cancer Res April 15 1991 (51) (8) 2151-2157;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Inhibition of Tumor Invasion of Smooth Muscle Cell Layers by Recombinant Human Metalloproteinase Inhibitor
Yves A. DeClerck, Tsuey-Dawn Yean, Darkin Chan, Hiroyuki Shimada and Keith E. Langley
Cancer Res April 15 1991 (51) (8) 2151-2157;
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
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Membership of Awards Assembly
  • Laureates
  • The Role of Chimeric Paired Box Transcription Factors in the Pathogenesis of Pediatric Rhabdomyosarcoma
Show more Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

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

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Research

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

Copyright © 2021 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