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Strategic Endothelial Cell Tube Formation Assay: Comparing Extracellular Matrix and Growth Factor Reduced Extracellular Matrix
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MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth

N E Sounni1, L Devy, A Hajitou

  • 1Laboratory of Tumor and Development Biology, Laboratory of Connective Tissues Biology, University of Liège, Sart Tilman, B-4000 Liège, Belgium.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|March 29, 2002
PubMed

Insights

Overexpressing membrane type 1 metalloprotease (MT1-MMP) in breast cancer cells enhances tumor growth and vascularization, independent of MMP-2. This highlights MT1-MMP

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Membrane type 1 metalloprotease (MT1-MMP) is crucial for extracellular matrix remodeling and activates pro-MMP-2.
  • MT1-MMP's role in tumor angiogenesis and invasiveness is not fully understood, especially in breast cancer cells lacking endogenous expression.

Purpose of the Study:

  • To investigate the impact of MT1-MMP overexpression on the in vitro and in vivo characteristics of human breast adenocarcinoma MCF7 cells.
  • To determine the role of MT1-MMP in tumor cell invasiveness, vascularization, and angiogenesis, with or without co-expression of MMP-2.

Main Methods:

  • Transfection of MT1-MMP and MMP-2 cDNAs into MCF7 cells.
  • Assessment of in vitro invasiveness using matrigel-coated filters.
  • Evaluation of tumor development and vascularization in vivo after subcutaneous injection into nude mice.
  • Analysis of blood vessel sprouting using the rat aortic ring assay.
  • Measurement of VEGF expression levels.

Main Results:

  • MT1-MMP overexpression enabled MCF7 cells to activate pro-MMP-2.
  • Enhanced in vitro invasiveness was observed, irrespective of MMP-2 co-expression.
  • MT1-MMP-expressing cells rapidly formed highly vascularized tumors in vivo.
  • MT1-MMP promoted blood vessel sprouting and was associated with increased VEGF expression, indicating an angiogenic phenotype.

Conclusions:

  • MT1-MMP overexpression significantly promotes tumor angiogenesis and invasiveness in breast cancer cells.
  • The pro-angiogenic effects of MT1-MMP are largely independent of tumor cell-derived MMP-2.
  • MT1-MMP is a key factor in tumor vascularization, suggesting its potential as a therapeutic target for anti-angiogenic strategies.

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