The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform

Kevin J Leco - One of the best experts on this subject based on the ideXlab platform.

  • Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type Matrix Metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas
    British Journal of Cancer, 1999
    Co-Authors: Peter A Forsyth, Huong Muzik, T D Laing, Penny M. A. Brasher, R N Johnston, Kevin J Leco, D G Morris, N. Barry Rewcastle, H Wong, G. Sutherland
    Abstract:

    Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis

  • gelatinase a mmp 2 gelatinase b mmp 9 and membrane type Matrix metalloproteinase 1 mt1 mmp are involved in different aspects of the pathophysiology of malignant gliomas
    British Journal of Cancer, 1999
    Co-Authors: Huong Muzik, T D Laing, Don Morris, Kevin J Leco, N. Barry Rewcastle, Peter A Forsyth, H Wong
    Abstract:

    Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis. © 1999 Cancer Research Campaign

Peter A Forsyth - One of the best experts on this subject based on the ideXlab platform.

  • Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type Matrix Metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas
    British Journal of Cancer, 1999
    Co-Authors: Peter A Forsyth, Huong Muzik, T D Laing, Penny M. A. Brasher, R N Johnston, Kevin J Leco, D G Morris, N. Barry Rewcastle, H Wong, G. Sutherland
    Abstract:

    Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis

  • gelatinase a mmp 2 gelatinase b mmp 9 and membrane type Matrix metalloproteinase 1 mt1 mmp are involved in different aspects of the pathophysiology of malignant gliomas
    British Journal of Cancer, 1999
    Co-Authors: Huong Muzik, T D Laing, Don Morris, Kevin J Leco, N. Barry Rewcastle, Peter A Forsyth, H Wong
    Abstract:

    Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis. © 1999 Cancer Research Campaign

Motoharu Seiki - One of the best experts on this subject based on the ideXlab platform.

  • membrane type Matrix metalloproteinase 1 mt1 mmp is a processing enzyme for human laminin γ2 chain
    Journal of Biological Chemistry, 2005
    Co-Authors: Tomoko Minegishi, Naohiko Koshikawa, Andrew B Sharabi, Vito Quaranta, Motoharu Seiki
    Abstract:

    Abstract Processing of the laminin-5 (Ln-5) γ2 chain by Membrane-Type-1 Matrix metalloproteinases (MT1-MMP) promotes migration and invasion of epithelial and tumor cells. We previously demonstrated that MT1-MMP cleaves the rat γ2 chain at two sites, producing two major C-terminal fragments of 100 (γ2′) and 80 (γ2x) kDa and releasing a 30-kDa fragment containing epidermal growth factor (EGF)-like motifs (domain III (DIII) fragment). The DIII fragment bound the EGF receptor (EGF-R) and stimulated cell scattering and migration. However, it is not yet clear whether human Ln-5 is processed in a similar fashion to rat Ln-5 because one of the two MT1-MMP cleavage sites present in rat γ2 is not found in human γ2. To identify the exact cleavage site for MT1-MMP in human Ln-5, we purified both the whole molecule as well as a monomeric form of human γ2 that is frequently expressed by malignant tumor cells. Like rat Ln-5, both the monomer of γ2, as well as the γ2 derived from intact Ln-5, were cleaved by MT1-MMP in vitro, generating C-terminal γ2′ (100 kDa) and γ2x (85 kDa) fragments and releasing DIII fragments (25 and 27k Da). In addition to the conserved first cleavage site used to generate γ2′, two adjacent cleavage sites (Gly559–Asp560 and Gly579–Ser580) were found that could generate the γ2x and DIII fragments. Two of the three EGF-like motifs present in the rat DIII fragment are present in the 27-kDa human fragment, and like the rat DIII, this fragment can promote breast carcinoma cell migration by engaging the EGF-R. These results suggest that MT1-MMP processing of Ln-5 in human tumors may stimulate the EGF-R, resulting in increased tumor cell scattering and migration that could possibly increase their metastatic potential.

  • identification of membrane type Matrix metalloproteinase 1 as a target of the β catenin tcf4 complex in human colorectal cancers
    Oncogene, 2002
    Co-Authors: Meiko Takahashi, Tatsuhiko Tsunoda, Motoharu Seiki, Yusuke Nakamura, Yoichi Furukawa
    Abstract:

    Identification of Membrane-Type Matrix Metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers

  • expression of membrane type Matrix metalloproteinase 1 mt1 mmp in tumor cells enhances pulmonary metastasis in an experimental metastasis assay
    Cancer Research, 1996
    Co-Authors: Yoshio Tsunezuka, Takahisa Takino, Hiroshi Sato, Hiroaki Kinoh, Yoh Watanabe, Yasunori Okada, Akira Shinagawa, Motoharu Seiki
    Abstract:

    Abstract Membrane-Type Matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique Membrane-Type subgroup in the Matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular Matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MTI-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neor gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.

  • membrane type Matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinases 2
    Cancer Research, 1996
    Co-Authors: Kazushi Imai, Hiroshi Sato, Motoharu Seiki, Eiko Ohuchi, Takanori Aoki, Hidehiro Nomura, Yutaka Fujii, Yasunori Okada
    Abstract:

    Abstract The processing mechanism and gelatinolytic activity of the membranetype Matrix metalloproteinase 1 (MT-MMP-1) were examined by expressing in COS-1 cells a deletion mutant of MT-MMP-1 lacking the transmembrane domain (ΔMT1) and its site-directed mutant with a furinresistant sequence in the propeptide domain (mutant ΔMT1). ΔMT1, but not mutant ΔMT1, was processed to an active form and exhibited gelatinolytic activity as seen using gelatin zymography. ΔMT1 isolated in a complex form with tissue inhibitor of metalloproteinases 2 (TIMP-2) from the stable transfectants demonstrated the NH 2 -terminal sequence of Ala 113 -IIe-Gln-Gly-Leu, indicating cleavage at one amino acid down-stream from the furin recognition sequence. The ΔMT1/TIMP-2 complex formed a ternary complex with proMMP-2 through the COOH termini of TIMP-2 and proMMP-2. A human breast carcinoma cell line (MDA-MB-231 cells) also secreted MT-MMP-1 into culture media, which was purified in a complex form with TIMP-2 and showed gelatinolytic activity as seen using zymography. These results demonstrate for the first time that MT-MMP-1 is a gelatinolytic enzyme and secreted from cells in a complex with TIMP-2, which can form a ternary complex of MT-MMP-1/TIMP-2/proMMP-2.

Haiyun Xu - One of the best experts on this subject based on the ideXlab platform.

  • multiple essential mt1 mmp functions in tooth root formation dentinogenesis and tooth eruption
    Matrix Biology, 2016
    Co-Authors: Haiyun Xu, T N Snider, Helen F Wimer, Susan S Yamada, Ting Yang, Kenn Holmbeck, Brian L Foster
    Abstract:

    Abstract Membrane-Type Matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular Matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice ( MT1-MMP −/− ) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated Matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region.

Hiroshi Sato - One of the best experts on this subject based on the ideXlab platform.

  • cleavage of lumican by membrane type Matrix metalloproteinase 1 abrogates this proteoglycan mediated suppression of tumor cell colony formation in soft agar
    Cancer Research, 2004
    Co-Authors: Yingyi Li, Yusaku Mori, Hisashi Miyamori, Munirah Ahmad, Takahisa Takino, Takeshi Aoki, Hiroshi Sato
    Abstract:

    The small leucine-rich proteoglycan lumican was identified from a human placenta cDNA library by the expression cloning method as a gene product that interacts with Membrane-Type Matrix Metalloproteinase-1 (MT1-MMP). Coexpression of MT1-MMP with lumican in HEK293T cells reduced the concentration of lumican secreted into culture medium, and this reduction was abolished by addition of the MMP inhibitor BB94. Lumican protein from bovine cornea and recombinant lumican core protein fused to glutathione S-transferase was shown to be cleaved at multiple sites by recombinant MT1-MMP. Transient expression of lumican in HEK293 cells induced expression of tumor suppressor gene product p21/Waf-1, which was abrogated by the coexpression of MT1-MMP concomitant with a reduction in lumican concentration in culture medium. Stable expression of lumican in HeLa cells induced expression of p21 and reduction of colony formation in soft agar, which were both abolished by the expression of MT1-MMP. HT1080 fibrosarcoma cells stably transfected with the lumican cDNA (HT1080/Lum), which express endogenous MT1-MMP, secreted moderate levels of lumican; however, treatment of HT1080/Lum cells with BB94 resulted in accumulation of lumican in culture medium. The expression levels of p21 in HT1080/Lum were proportional to the concentration of secreted lumican and showed reverse corelation with colony formation in soft agar. These results suggest that MT1-MMP abrogates lumican-mediated suppression of tumor cell colony formation in soft agar by degrading this proteoglycan, which down-regulates it through the induction of p21.

  • Cleavage of syndecan-1 by Membrane-Type Matrix Metalloproteinase-1 stimulates cell migration
    Journal of Biological Chemistry, 2003
    Co-Authors: Kazuhira Endo, Hisashi Miyamori, Takahisa Takino, Hidenori Kinsen, Tomokazu Yoshizaki, Mitsuru Furukawa, Hiroshi Sato
    Abstract:

    The transmembrane heparan sulfate proteoglycan syndecan-1 was identified from a human placenta cDNA library by the expression cloning method as a gene product that interacts with membrane type Matrix Metalloproteinase-1 (MT1-MMP). Co-expression of MT1-MMP with syndecan-1 in HEK293T cells promoted syndecan-1 shedding, and concentration of cell-associated syndecan-1 was reduced. Treatment of cells with MMP inhibitor BB-94 or tissue inhibitor of MMP (TIMP)-2 but not TIMP-1 interfered with the syndecan-1 shedding promoted by MT1-MMP expression. In contrast, syndecan-1 shedding induced by 12-O-tetradecanoylphorbol-13-acetate treatment was inhibited by BB-94 but not by either TIMP-1 or TIMP-2. Shedding of syndecan-1 was also induced by MT3-MMP but not by other MT-MMPs. Recombinant syndecan-1 core protein was shown to be cleaved by recombinant MT1-MMP or MT3-MMP preferentially at the Gly245-Leu246 peptide bond. HT1080 fibrosarcoma cells stably transfected with the syndecan-1 cDNA (HT1080/SDC), which express endogenous MT1-MMP, spontaneously shed syndecan-1. Migration of HT1080/SDC cells on collagen-coated dishes was significantly slower than that of control HT1080 cells. Treatment of HT1080/SDC cells with BB-94 or TIMP-2 induced accumulation of syndecan-1 on the cell surface, concomitant with further retardation of cell migration. Substitution of Gly245 of syndecan-1 with Leu significantly reduced shedding from HT1080/SDC cells and cell migration. These results suggest that the shedding of syndecan-1 promoted by MT1-MMP through the preferential cleavage of Gly245-Leu246 peptide bond stimulates cell migration.

  • expression of membrane type Matrix metalloproteinase 1 mt1 mmp in tumor cells enhances pulmonary metastasis in an experimental metastasis assay
    Cancer Research, 1996
    Co-Authors: Yoshio Tsunezuka, Takahisa Takino, Hiroshi Sato, Hiroaki Kinoh, Yoh Watanabe, Yasunori Okada, Akira Shinagawa, Motoharu Seiki
    Abstract:

    Abstract Membrane-Type Matrix metalloproteinase 1 (MT1-MMP) is a member of the recently identified unique Membrane-Type subgroup in the Matrix metalloproteinase (MMP) family. MT1-MMP has proteolytic activity against components in the extracellular Matrix and activates progelatinase A (72-kDa type IV procollagenase/proMMP-2) on the cell surface. Because MT1-MMP is frequently expressed in a variety of tumors, we examined its contribution to their metastatic potential. The mouse lung carcinoma cell line Madison 109 was transiently transfected with a MTI-MMP expression plasmid and inoculated into the tail vein of BALB/c mouse. Fate of the transfected cells was monitored by the neor gene in the plasmid using the quantitative PCR method. The survival rate of the parental cells in lung was 0.7% of the inoculated cells. It was increased by 3-fold with the MT1-MMP transfected cells and the number of the lung nodules increased accordingly. Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1-MMP-negative cells were not stained for gelatinase A at all. Thus, MT1-MMP-expressing cells acquire specific ability to bind exogenous progelatinase A.

  • membrane type Matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinases 2
    Cancer Research, 1996
    Co-Authors: Kazushi Imai, Hiroshi Sato, Motoharu Seiki, Eiko Ohuchi, Takanori Aoki, Hidehiro Nomura, Yutaka Fujii, Yasunori Okada
    Abstract:

    Abstract The processing mechanism and gelatinolytic activity of the membranetype Matrix metalloproteinase 1 (MT-MMP-1) were examined by expressing in COS-1 cells a deletion mutant of MT-MMP-1 lacking the transmembrane domain (ΔMT1) and its site-directed mutant with a furinresistant sequence in the propeptide domain (mutant ΔMT1). ΔMT1, but not mutant ΔMT1, was processed to an active form and exhibited gelatinolytic activity as seen using gelatin zymography. ΔMT1 isolated in a complex form with tissue inhibitor of metalloproteinases 2 (TIMP-2) from the stable transfectants demonstrated the NH 2 -terminal sequence of Ala 113 -IIe-Gln-Gly-Leu, indicating cleavage at one amino acid down-stream from the furin recognition sequence. The ΔMT1/TIMP-2 complex formed a ternary complex with proMMP-2 through the COOH termini of TIMP-2 and proMMP-2. A human breast carcinoma cell line (MDA-MB-231 cells) also secreted MT-MMP-1 into culture media, which was purified in a complex form with TIMP-2 and showed gelatinolytic activity as seen using zymography. These results demonstrate for the first time that MT-MMP-1 is a gelatinolytic enzyme and secreted from cells in a complex with TIMP-2, which can form a ternary complex of MT-MMP-1/TIMP-2/proMMP-2.