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Related Experiment Videos

Functional interplay between type I collagen and cell surface matrix metalloproteinase activity.

S M Ellerbroek1, Y I Wu, C M Overall

  • 1Department of Cell and Molecular Biology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611, USA.

The Journal of Biological Chemistry
|May 2, 2001
PubMed
Summary

Ovarian cancer cells activate pro-matrix metalloproteinase (pro-MMP)-2 via beta(1) integrin clustering, a process crucial for collagen invasion. This activation is mediated by membrane-type 1 (MT1)-MMP, highlighting its role in cancer cell motility.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Type I collagen stimulates pro-matrix metalloproteinase (pro-MMP)-2 activation in ovarian cancer cells through beta(1) integrin receptor clustering.
  • The precise cellular and biochemical mechanisms governing MMP processing during this activation remain incompletely understood.

Purpose of the Study:

  • To elucidate the specific cellular and biochemical events involved in collagen-induced pro-MMP-2 activation by ovarian cancer cells.
  • To investigate the role of integrin subtypes and membrane-type 1 (MT1)-MMP in this process and its contribution to cellular invasion.

Main Methods:

  • Utilized DOV13 ovarian cancer cells and type I collagen matrices.
  • Employed antibody-induced integrin clustering (alpha(2)beta(1) and alpha(3)beta(1)) to study pro-MMP-2 activation.

Related Experiment Videos

  • Analyzed cell surface expression and localization of MT1-MMP.
  • Assessed cellular invasion assays in the presence of inhibitors and modified collagen.
  • Main Results:

    • Collagenolysis is not required for pro-MMP-2 activation; intact collagen binding is essential.
    • Alpha(3)beta(1) integrin clustering significantly enhances pro-MMP-2 activation, while alpha(2)beta(1) has minimal effect.
    • Integrin clustering increases MT1-MMP cell surface expression and co-localization with integrin complexes.
    • MT1-MMP undergoes autolysis on the cell surface, independent of active MMP-2.
    • Cellular invasion of collagen matrices depends on collagenase activity and is inhibited by TIMP-2 and collagenase-resistant collagen.

    Conclusions:

    • Integrin-mediated MT1-MMP activity is a critical determinant of ovarian cancer cell invasion through type I collagen.
    • The findings provide a mechanistic insight into how MT1-MMP activity is regulated during collagen degradation and cellular invasion.