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

Barbara Fingleton, Tracy Vargo-Gogola, Howard C. Crawford, Lynn M. Matrisian

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)459-468
Number of pages10
JournalNeoplasia
Volume3
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 7
Matrix Metalloproteinases
Apoptosis
Neoplasms
Cell Line
Apoptosis Regulatory Proteins
Fas Ligand Protein
Neutralizing Antibodies
Cell Death
Antibodies
Enzymes

Keywords

  • Drug resistance
  • Fas ligand
  • Immune surveillance
  • Matrix metalloproteinase
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research

Cite this

Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. / Fingleton, Barbara; Vargo-Gogola, Tracy; Crawford, Howard C.; Matrisian, Lynn M.

In: Neoplasia, Vol. 3, No. 6, 2001, p. 459-468.

Research output: Contribution to journalArticle

Fingleton, Barbara ; Vargo-Gogola, Tracy ; Crawford, Howard C. ; Matrisian, Lynn M. / Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. In: Neoplasia. 2001 ; Vol. 3, No. 6. pp. 459-468.
@article{1489bcdb1d884ee8890ead3141cfd780,
title = "Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis",
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.",
keywords = "Drug resistance, Fas ligand, Immune surveillance, Matrix metalloproteinase, Tumor progression",
author = "Barbara Fingleton and Tracy Vargo-Gogola and Crawford, {Howard C.} and Matrisian, {Lynn M.}",
year = "2001",
doi = "10.1038/sj.neo.7900190",
language = "English (US)",
volume = "3",
pages = "459--468",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis

AU - Fingleton, Barbara

AU - Vargo-Gogola, Tracy

AU - Crawford, Howard C.

AU - Matrisian, Lynn M.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Drug resistance

KW - Fas ligand

KW - Immune surveillance

KW - Matrix metalloproteinase

KW - Tumor progression

UR - http://www.scopus.com/inward/record.url?scp=0035216956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035216956&partnerID=8YFLogxK

U2 - 10.1038/sj.neo.7900190

DO - 10.1038/sj.neo.7900190

M3 - Article

VL - 3

SP - 459

EP - 468

JO - Neoplasia

JF - Neoplasia

SN - 1522-8002

IS - 6

ER -