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PMID: 11774028 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Neoplasia (New York, N.Y.) ·Vol. 3 ·No. 6 ·2001-00-00 ·Pages 459-68

Fingleton B, Vargo-Gogola T, Crawford HC, Matrisian LM

Abstract

The matrix metalloproteinase matrilysin (MMP-7) has been demonstrated to contribute to tumor development. We have shown previously that members of the TNF family of apoptosis-inducing proteins are substrates for this enzyme, resulting in increased death pathway signaling. The goal of the current study was to reconcile the proapoptotic and tumor-promoting functions of matrilysin. In the human HBL100 and murine NMuMG cell lines that represent early stages of tumor progression and that express both Fas ligand and its receptor, exposure to matrilysin results in cell death that can be blocked by FasL neutralizing antibodies. Constitutive expression of matrilysin in these cell lines selects for cells with reduced sensitivity to Fas-mediated apoptosis as demonstrated both with a receptor-activating antibody and with in vitro activated splenocytes. Matrilysin-expressing cells are also significantly less sensitive to chemical inducers of apoptosis. We propose that the expression of matrilysin that has been reported at early stages in various tumor types can act to select cells with a significantly decreased chance of removal due to immune surveillance. As a result, these cells are more likely to acquire additional genetic modifications and develop further as tumors.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology Apoptosis/physiology Breast/cytology Clone Cells/cytology,drug effects,enzymology Concanavalin A/pharmacology Cycloheximide/pharmacology DNA, Complementary/genetics Enzyme Induction Enzyme Inhibitors/pharmacology Epithelial Cells/cytology,drug effects,enzymology Fas Ligand Protein Female Humans Interleukin-2/pharmacology Killer Cells, Natural/immunology Lymphocyte Activation/drug effects Male Mammary Glands, Animal/cytology Matrix Metalloproteinase 7/genetics,physiology Membrane Glycoproteins/antagonists & inhibitors,pharmacology,physiology Mice Mitomycin/pharmacology Protein Synthesis Inhibitors/pharmacology Rabbits Rats Recombinant Fusion Proteins/physiology Spleen/cytology Staurosporine/pharmacology T-Lymphocytes/drug effects,immunology Transfection fas Receptor/physiology
Chemicals
Antibodies, Monoclonal DNA, Complementary Enzyme Inhibitors FASLG protein, human Fas Ligand Protein Fasl protein, mouse Faslg protein, rat Interleukin-2 Membrane Glycoproteins Protein Synthesis Inhibitors Recombinant Fusion Proteins fas Receptor Concanavalin A Mitomycin Cycloheximide Matrix Metalloproteinase 7 Staurosporine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fingleton B
Department of Cancer Biology, Vanderbilt University School of Medicine, PRB 23rd and Pierce, Nashville, TN 37232-6840, USA. barbara.fingleton@mcmail.vanderbilt.edu
Vargo-Gogola T
Crawford H C
Matrisian L M
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1038/sj.neo.7900190
Email
barbara.fingleton@mcmail.vanderbilt.edu
Published
2001-00-00
Pages
459-68
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1506562
Subset
IM
Grants
NCI NIH HHS · P30 CA068485 · United States
NCI NIH HHS · R01 CA060867 · United States
NCI NIH HHS · P30 CA68485 · United States
NCI NIH HHS · R01 CA60867 · United States
External Links
PubMed source DOI: 10.1038/sj.neo.7900190 PMC Full Text
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