title: 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 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.
authors.affiliation: First Department of Internal Medicine, Obere Zahlbacher Str 63, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Vijay
authors.initials: V
authors.lastname: Alla
authors.forename: Anubha
authors.initials: A
authors.lastname: Kashyap
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gregor
authors.forename: Matthias
authors.initials: M
authors.lastname: Theobald
authors.forename: Hans
authors.initials: H
authors.lastname: Heid
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Dennis
authors.initials: D
authors.lastname: Strand
authors.forename: Susanne
authors.initials: S
authors.lastname: Strand
mesh_terms: 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
chemical_list: D004317:Doxorubicin; D019272:Leukocyte Elastase; D020783:Matrix Metalloproteinase 7