0000000000067854
AUTHOR
Hans Heid
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.
Cleavage of CD95 by matrix metalloproteinase-7 induces apoptosis resistance in tumour cells
The ability of tumour cells to resist apoptosis-inducing signals by cytotoxic T cells may decide the success or failure of tumour elimination. An important effector of apoptosis is the CD95/CD95 ligand system (APO-1/Fas) that mediates perforin-independent cytotoxic T-cell killing of tumour cells. We propose a new strategy by which tumour cells can resist CD95-induced apoptosis. We identified matrix metalloproteinase-7, MMP-7 (Martilysin), as the first physiologically relevant protease that can specifically cleave CD95. MMP-7 is of unique importance because it is produced by the tumour cells themselves at early stages of tumour development. Microsequencing of the positions in CD95 cleaved by…
Distribution of a special subset of keratinocytes characterized by the expression of cytokeratin 9 in adult and fetal human epidermis of various body sites.
Biochemical analyses have previously shown that palmar and plantar epidermis, unlike the epidermis of other body sites, contain cytokeratin 9 (Mr 64,000), an unusually large acidic (type I) cytokeratin. Guinea-pig antibodies that specifically and selectively react with bovine and human cytokeratin 9 were used for the immunocytochemical identification of cytokeratin 9 in adult and fetal human epidermis from various body sites. In the epidermis of palms and soles, antibodies against cytokeratin 9 stained a high proportion of the keratinocytes in suprabasal locations. These suprabasal cytokeratin-9-positive keratinocytes were often arranged in vertical columns and concentrated around intraepid…
Cytokeratin Analysis of Pilomatrixoma: Changes in Cytokeratin-Type Expression During Differentiation
The various structural components of pilomatrixoma (calcifying epithelioma of Malherbe) were studied for the expression of hair-specific (trichocytic) cytokeratins as well as epithelial cytokeratins, using immunoperoxidase as well as epithelial cytokeratins, using immunoperoxidase and immunofluorescence microscopy of frozen sections as well as two-dimensional gel electrophoresis and immunoblotting. Trichocyte-type cytokeratins were detected in only a minor subpopulation of basophilic cells but more prominently in most “transitional” cells as well as in “shadow” cells. in contrast, antibodies against certain epithelial cytokeratins (including antibody KA1 against cytokeratins of stratified s…
Patterns of expression of trichocytic and epithelial cytokeratins in mammalian tissues
Abstract Cells forming hair and nail material are characterized by the synthesis of members of a particular group of α-keratin polypeptides (trichocytic cytokeratins, “T cytokeratins”) different from epithelial cytokeratins (“E cytokeratins”). As the precursor cells to trichocytes are derived from fetal epidermal keratinocytes expressing only E cytokeratins, we have studied the patterns of expression of both T and E cytokeratins in developing human hair-and nailforming tissues of different fetal stages, by immunocyto-chemistry using antibodies specific for certain T or E cytokeratins and by two-dimensional gel electrophoresis and immunoblotting. In developing hair follicles up to the early …