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Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis

B Fingleton1, T Vargo-Gogola, H C Crawford

  • 1Department of Cancer Biology, Vanderbilt University School of Medicine, PRB 23rd and Pierce, Nashville, TN 37232-6840, USA. barbara.fingleton@mcmail.vanderbilt.edu

Neoplasia (New York, N.Y.)
|January 5, 2002
PubMed

Insights

Matrilysin (MMP-7) promotes tumor development by reducing cancer cell sensitivity to apoptosis, allowing cells to evade immune surveillance and acquire mutations for further tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Matrilysin (MMP-7) is implicated in tumor development.
  • TNF-family proteins are substrates for MMP-7, influencing apoptosis.
  • MMP-7 exhibits both pro-apoptotic and tumor-promoting functions.

Purpose of the Study:

  • To reconcile the dual roles of matrilysin (MMP-7) in apoptosis and tumor promotion.
  • To investigate MMP-7's impact on cancer cell sensitivity to death receptor-mediated apoptosis.

Main Methods:

  • Utilized human HBL100 and murine NMuMG cell lines representing early tumor progression.
  • Assessed cell death upon matrilysin exposure, blocked by FasL neutralizing antibodies.
  • Evaluated Fas-mediated apoptosis sensitivity in matrilysin-expressing cells using receptor-activating antibodies and splenocytes.
  • Tested sensitivity to chemical apoptosis inducers in matrilysin-expressing cells.

Main Results:

  • Matrilysin exposure induced cell death in HBL100 and NMuMG cells, inhibited by FasL antibodies.
  • Constitutive matrilysin expression selected for cells with reduced sensitivity to Fas-mediated apoptosis.
  • Matrilysin-expressing cells demonstrated significantly lower sensitivity to chemical apoptosis inducers.

Conclusions:

  • Early-stage tumor expression of matrilysin (MMP-7) selects for apoptosis-resistant cells.
  • This resistance may allow cells to evade immune surveillance, promoting tumor progression.
  • MMP-7 contributes to tumor development by facilitating the acquisition of further genetic modifications.

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