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  • 1
    ISSN: 1573-7276
    Keywords: invasion ; metalloproteinases ; metastasis ; tissue inhibitors of metalloproteinases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT)in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at Mr 121000, 92000, and 72000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 bothin vitro andin vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7276
    Keywords: glioblastoma multiforme ; invasion ; matrix ; metalloproteinases ; metastasis ; tissue inhibitors of metalloproteinases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tissue inhibitors of metalloproteinases (TIMPs) are negative regulators of matrix metalloproteinases (MMPs) which degrade major components of the extracellular matrix. The aberrant expression of TIMPs is believed to represent an important modulating factor in the invasive capacity of human tumors. In the present study we analyzed the expression of TIMPs in human brain tumor tissue samples by an enzyme-linked immunosorbent assay (ELISA) and by Northern blotting analysis. Quantitation of TIMP-1 and TIMP-2 by ELISA demonstrated low levels of TIMP-1 and TIMP-2 proteins in glioblastomas, and moderate levels in anaplastic astrocytomas compared with normal brain tissues low-grade gliomas and metastatic tumors (renal and breast carcinomas and melanomas). Northern blot analysis of TIMP-1 transcripts demonstrated higher expression in meningioma, normal brain tissues and other metastatic tumors than in anaplastic astrocytoma and glioblastoma. Two distinct transcripts of 1.0 and 3.5 kb were observed for TIMP-2 mRNA in normal brain tissue and in tumor extracts. In addition, TIMP-2 mRNA expression was lower in glioblastoma and anaplastic astrocytoma than in meningioma, normal brain tissues and metastatic tumors. These findings suggest that down-regulation of both TIMP-1 and TIMP-2 contributes significantly to the invasive potential of human glioblastoma multiforme and anaplastic astrocytomas.
    Type of Medium: Electronic Resource
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