Expression of matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP) and their inhibitors (TIMP-1, TIMP-2) in common epithelial tumors of the ovary. 2000

K Sakata, and K Shigemasa, and N Nagai, and K Ohama
Department of Obstetrics and Gynecology, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8551, Japan.

Matrix metalloproteinases (MMPs) are known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix proteins. The activity of such MMPs are regulated by tissue inhibitors of metalloproteinases (TIMPs). In this study, we investigated the immunohistochemical expression of MMP-2, MT1-MMP, TIMP-2, MMP-9, and TIMP-1 in 114 epithelial ovarian tumors (14 adenomas, 22 borderline tumors, and 78 adenocarcinomas). mRNA expression of MMP-2, MT1-MMP, and TIMP-2 was determined by RT-PCR in selected samples. The diffuse positive rates of MMP-2, MT1-MMP, TIMP-2, and MMP-9 in ovarian carcinomas were significantly higher than those in the borderline and in benign tumors. Conversely, the diffuse positive rate of TIMP-1 was higher in the benign and borderline ovarian tumors than that in ovarian carcinomas. The percentages of the cases with triple diffuse positive expression for MMP-2, MT1-MMP, and TIMP-2 within the same tumor was significantly higher in malignant tumors than those in borderline and in benign tumors. With respect to clinical stage, the triple diffuse positive rate in advanced-stage (stage II/III/IV) carcinomas was significantly higher than that in early-stage (stage I) carcinomas. A significantly higher triple diffuse positive rate was also observed in high-grade (grade 2/3) disease than in low-grade (grade 1) disease. Considerable levels of mRNA expression of MMP-2, MT1-MMP and TIMP-2 were detected in all selected samples that showed triple diffuse positive immunostaining, confirming the co-expression of MMP-2, MT1-MMP, and TIMP-2 at the transcriptional level within the same tumor. All cases with diffuse positive expression for MMP-9 showed regional or negative TIMP-1 expression. The diffuse positive rate of MMP-9 was significantly higher in ovarian carcinomas with lymph node metastasis than in those without lymph node metastasis. Our results suggest that the overexpression of MMP-2, MT1-MMP, TIMP-2, and MMP-9 and down-regulation of TIMP-1 may contribute to the development or enhanced growth capacity of ovarian tumors. Co-expression of MMP-2, MT1-MMP, and TIMP-2 within the same tumor seems to play an important role in the progression of ovarian cancer. Elevated MMP-9 expression together with low expression of TIMP-1 may also contribute to the lymph node metastasis of ovarian carcinoma cells.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D009375 Neoplasms, Glandular and Epithelial Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue. Epithelial Cell Neoplasms,Glandular Cell Neoplasms,Epithelial Neoplasms,Glandular Neoplasms,Glandular and Epithelial Neoplasms,Neoplasms, Epithelial,Neoplasms, Glandular,Neoplasms, Glandular Epithelial,Cell Neoplasm, Epithelial,Cell Neoplasm, Glandular,Cell Neoplasms, Epithelial,Epithelial Cell Neoplasm,Epithelial Neoplasm,Epithelial Neoplasm, Glandular,Glandular Cell Neoplasm,Glandular Epithelial Neoplasm,Glandular Epithelial Neoplasms,Glandular Neoplasm,Neoplasm, Epithelial,Neoplasm, Epithelial Cell,Neoplasm, Glandular,Neoplasm, Glandular Cell,Neoplasm, Glandular Epithelial
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D053504 Matrix Metalloproteinases, Membrane-Associated Matrix metalloproteinases that are associated with the CELL MEMBRANE, either through transmembrane domains or GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS. Membrane-type matrix metalloproteinases may act within the pericellular environment to influence the process of CELL MIGRATION. Membrane-Type Matrix Metalloproteinase,MT-MMP Enzymes,Matrix Metalloproteinase, Membrane-Type,Membrane-Type Matrix Metalloproteinases,MT MMP Enzymes,Matrix Metalloproteinase, Membrane Type,Matrix Metalloproteinases, Membrane Associated,Matrix Metalloproteinases, Membrane-Type,Membrane Type Matrix Metalloproteinase,Membrane Type Matrix Metalloproteinases,Membrane-Associated Matrix Metalloproteinases,Metalloproteinase, Membrane-Type Matrix,Metalloproteinases, Membrane-Associated Matrix,Metalloproteinases, Membrane-Type Matrix

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