Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells.
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.
Alla
Vijay
V
First Department of Internal Medicine, Obere Zahlbacher Str 63, Johannes Gutenberg-University, Mainz, Germany.
Kashyap
Anubha
A
Gregor
Sebastian
S
Theobald
Matthias
M
Heid
Hans
H
Galle
Peter R
PR
Strand
Dennis
D
Strand
Susanne
S
D017209:Apoptosis; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000502:physiology*; D020783:Matrix Metalloproteinase 7 / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004317:Doxorubicin; D019272:Leukocyte Elastase; D020783:Matrix Metalloproteinase 7