Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells

Abstract Matrix metalloproteinase-7 (MMP-7/Matrilysin) is a component of the tumor microenvironment associated with malignant progression. Its expression in tumors protects tumor cells from CD95-mediated apoptosis and the cytotoxic activity of tumor specific CD8+ T cells. In the present study, we sh...

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Bibliographic Details
Published in:Cancer letters 2008-09, Vol.268 (2), p.331-339
Main Authors: Alla, Vijay, Kashyap, Anubha, Gregor, Sebastian, Theobald, Matthias, Heid, Hans, Galle, Peter R, Strand, Dennis, Strand, Susanne
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis resistance
Cancer
Cancer therapies
Cells, Cultured
Chemokines
Chemotherapy
Clinical trials
Cytotoxic T lymphocytes
Cytotoxicity
Doxorubicin - pharmacology
Hematology, Oncology and Palliative Medicine
Humans
Immunotherapy
Infections
Leukocyte Elastase - physiology
Leukocytes
Matrix Metalloproteinase 7 - physiology
Medical research
MMP-7
Neoplasms - pathology
Neutrophil elastase
Neutrophils - physiology
Physiology
Proteins
Rodents
Surveillance
T-Lymphocytes, Cytotoxic - immunology
Tumors
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Summary:Abstract Matrix metalloproteinase-7 (MMP-7/Matrilysin) is a component of the tumor microenvironment associated with malignant progression. Its expression in tumors protects tumor cells from CD95-mediated apoptosis and the cytotoxic activity of tumor specific CD8+ T cells. In the present study, we show that human leukocyte elastase (HLE) secreted by polymorphonuclear leukocytes cleaves MMP-7 resulting in loss of enzymatic activity. The anti-apoptotic effect of MMP-7 is reduced in the presence of HLE for CD95-, doxorubicin- and CTL-mediated apoptosis. Our data indicates that HLE may be a natural inactivator of MMP-7 which can counteract MMP-7-induced apoptosis resistance.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.04.006