Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A non-metastatic epithelial tumor cell line, OV3121, was established from ovarian granulosa cell tumor in B6C3F1 mouse irradiated with 60Co-gamma rays. OV3121 cells showed an epithelial morphology and grew in monolayer with a population doubling time of 28-30 h. The production of estradiol and the expression of cytokeratin confirmed the epithelial origin of the line. No pulmonary metastasis was observed from solid tumors after subcutaneous (s.c.) injection or after intravenous (i.v.) injection of a clonal subline, OV3121-1 cells. We examined the experimental metastasis of individual clones of OV3121-1 cells, containing various introduced viral oncogenes: v-Ha-ras, v-Ki-ras, v-fms, v-mos, v-raf, v-src, v-sis, v-fos and v-myc. Among them, only OV3121-1 cells with v-Ha-MuSV or v-Ki-MuSV produced lung colonies at high frequencies. In a more detailed analysis, the v-Ha-ras transfectants OV-ras4 and OV-ras7 were found to form colonies in various organs by metastasis from tumors after s.c. injection, as well as lung colonies after i.v. injection. Moderately metastatic OV-ras7 cells showed high gelatinolytic activity at 72 kDa (MMP-2) and 92 kDa (MMP-9) as compared with the parental OV3121-1 and OV-Neo control cells by zymographic analysis. However, more metastatic OV-ras4 cells produced progressively weaker bands of 72 kDa gelatinolytic activity. No gross alterations in the expression of MMP-1, MMP-3, TIMP-1 and TIMP-2 transcripts were detected in these cell lines. These results suggest that this ovarian granulosa cell tumor line may provide a useful system for understanding the mechanisms by which oncogenes influence the occurrence of metastasis.
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PMID:A radiation-induced murine ovarian granulosa cell tumor line: introduction of v-ras gene potentiates a high metastatic ability. 777 56

Matrix metalloproteinase (MMP) family members have been associated with advanced-stage cancer and contribute to tumor progression, invasion, and metastasis as determined by inhibitor studies. In situ hybridization was performed to analyze the expression and localization of all known MMPs in a series of human breast cancer biopsy specimens. Most MMPs were localized to tumor stroma, and all MMPs had very distinct expression patterns. Matrilysin was expressed by morphologically normal epithelial ducts within tumors and in tissue from reduction mammoplasties, and by epithelial-derived tumor cells. Many family members, including stromelysin-3, gelatinase A, MT-MMP, interstitial collagenase, and stromelysin-1 were localized to fibroblasts of tumor stroma of invasive cancers but in quite distinct, and generally widespread, patterns. Gelatinase B, collagenase-3, and metalloelastase expression were more focal; gelatinase B was primarily localized to endothelial cells, collagenase-3 to isolated tumor cells, and metalloelastase to cytokeratin-negative, macrophage-like cells. The MMP inhibitor, TIMP-1, was expressed in both stromal and tumor components in most tumors, and neither stromelysin-2 nor neutrophil collagenase were detected in any of the tumors. These results indicate that there is very tight and complex regulation in the expression of MMP family members in breast cancer that generally represents a host response to the tumor and emphasize the need to further evaluate differential functions for MMP family members in breast tumor progression.
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PMID:Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. 868 51

A specialized subset of invasive embryonic cytotrophoblast cells gains access to maternal uterine arteries early in the gestation of higher primates. These cells continue to migrate extensively within the lumina of spiral arteries, converting them to the highly modified uteroplacental arteries of pregnancy. Although trophoblast cell-mediated modifications are considered critical to the progress of normal pregnancy, few studies have addressed the cellular interactions between maternal arteries and embryonic cells in situ. Macaque placentas and endometrial tissues were collected from 12 animals from day 14 of gestation (blastocyst implantation begins on day 9) to day 49. Standard indirect immunoperoxidase methods were used to identify matrix metalloproteinases (MMP-1, MMP-3, MMP-9), cathepsin B, cathepsin D, platelet-endothelial cell adhesion molecule, cytokeratins, smooth muscle actin, CD68, and factor VIII-related antigen. Cytotrophoblast cells were located deep within spiral arteries in each of the specimens examined. In some examples tightly packed clusters of cytotrophoblast occluded the lumina of invaded arteries. Initial penetration of arterial tunica intima was revealed by discontinuities in the staining pattern for factor VIII and cytotrophoblast intrusion was indicated by cytokeratin staining of the trophoblast cells. Continued cytotrophoblast intrusion into the tunica media was apparent by gaps in the smooth muscle. MMP-1, MMP-3, and MMP-9 were localized within intraluminal and intramural cytotrophoblast. By contrast, neither cathepsin B nor cathepsin D were present, although both were seen in uterine macrophages and stromal cells. Upon reaching the surrounding uterine stroma the cytotrophoblast cells ceased migration. As cytotrophoblast accumulated in the arterial wall the vascular lumen expanded. Evidence of cell death was rarely encountered in associated maternal or embryonic tissues. We conclude that intra-arterial cytotrophoblast cells express several proteinases with substrate specificities sufficient to permit independent remodeling of the extracellular matrix comprising uterine artery walls. The remodeling of the arteries, which involves extensive displacement of maternal endothelium and smooth muscle, in addition to degradation and synthesis of extracellular matrix, is accomplished with little evidence of cell death or loss of the integrity of the arteries. This process provides an interesting example of cooperation between different types of interacting tissues from genetically distinct individuals.
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PMID:Trophoblast cell-mediated modifications to uterine spiral arteries during early gestation in the macaque. 941 53

Studies have suggested the reversibility of liver fibrosis, but the mechanisms of fibrosis reversal are poorly understood. We investigated the possible functional link between apoptosis, macrophages, and matrix turnover in rat liver during reversal of fibrosis secondary to bile duct ligation (BDL). Biliary fibrosis was induced by BDL for 4 wk. After Roux-en-Y (RY)-bilio-jejunal-anastomosis, resolution of fibrosis was monitored for up to 12 wk by hepatic collagen content, matrix metalloproteinase (MMP) expression and activities, and fibrosis-related gene expression. MMP expression and activities were studied in macrophages after engulfment of apoptotic cholangiocytes in vitro. Hepatic collagen decreased to near normal at 12 wk after RY-anastomosis. During reversal, profibrogenic mRNA declined, whereas expression of several profibrolytic MMPs increased. Fibrotic septa showed fragmentation at week 4 and disappeared at week 12. Peak histological remodeling at week 4 was characterized by massive apoptosis of cytokeratin 19+ cholangiocytes, >90% in colocalization with CD68+ macrophages, and a 2- to 7.5-fold increase in matrix-degrading activities. In vitro, phagocytosis of apoptotic cholangiocytes induced matrix-degrading activities and MMP-3, -8, and -9 in rat peritoneal macrophages. We concluded that reconstruction of bile flow after BDL leads to an orchestrated fibrolytic program that results in near complete reversal of advanced fibrosis. The peak of connective tissue remodeling and fibrolytic activity is associated with massive apoptosis of cholangiocytes and their phagocytic clearance by macrophages in vivo. Macrophages upregulate MMPs and become fibrolytic effector cells upon apoptotic cholangiocyte engulfment in vitro, suggesting that phagocytosis-associated MMP induction in macrophages significantly contributes to biliary fibrosis reversal.
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PMID:Macrophage-mediated phagocytosis of apoptotic cholangiocytes contributes to reversal of experimental biliary fibrosis. 2005 96