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

Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF-alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect on tumor cell migration or invasion. The zymography of tumor conditioned medium showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in increases of type IV collagenase, stromelysin and urokinase-type plasminogen activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase (dThdPase) expression of tumor cells and consequently enhanced the antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by dThdPase. E2 and Prog did not have significant effects on the expression of proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells. The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory action on the motility of tumor cells. These results suggest that EGF and TGF-alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to invade extracellular matrices and their dThdPase expression, both of which are associated with the specific action of 5'-dFUrd selectively to kill tumor cells with high invasive and metastatic potential.
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PMID:Effects of sex steroids and growth factors on invasive activity and 5'-deoxy-5-fluorouridine sensitivity in ovarian adenocarcinoma OMC-3 cells. 1008 95

We investigated the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on migration, invasion and proteinase expression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarcinoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors affect thymidine phosphorylase/platelet-derived endothelial cell growth factor expression of tumor cells. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-alpha resulted in the increase of type IV collagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor which has angiogenic activity, was also upregulated by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of gynecological tumor cells which may be associated with their stimulatory action on the motility of tumor cells, the expression of proteinases secreted by tumor cells and the angiogenic phenotype.
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PMID:Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells. 1054 52

ADAMTS5 is a member of the A Disintegrin-like And Metalloproteinase with ThromboSpondin motifs (ADAMTS) family of secreted metalloproteinases with multiple proteoglycan substrates. Although well characterized for its role in cartilage degradation and arthritis, how it influences cancer remains unclear. We have previously shown that the first thrombospondin type 1 repeat (TSR1, the central TSR) but not TSR2 (the C-terminal TSR) of ADAMTS5 is anti-angiogenic in vitro. Coupled with previous reports that ADAMTS5 expression is altered in several human cancers, we hypothesized that this proteoglycanase may play an important role in cancer and angiogenesis. Here, we demonstrated that overexpression of full-length ADAMTS5 suppressed B16 melanoma growth in mice. The reduced tumor growth is correlated with diminished tumor angiogenesis, together with reduced tumor cell proliferation and increased tumor cell apoptosis. Catalytically active ADAMTS5 proteolytic fragment also suppressed angiogenesis in vitro. The catalytic activity of ADAMTS5 is dispensable for its anti-tumorigenic function, as the full-length active site mutant E411A presented similar tumor suppression activity. Domain mapping and mechanistic studies revealed that ADAMTS5 inhibits B16 tumorigenesis through its TSR1 by suppressing tumor angiogenesis, likely by down-regulating pro-angiogenic factors such as vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and platelet-derived endothelial growth factor (PD-ECGF) in the tumor milieu. This is the first report that ADAMTS5 is an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity.
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PMID:ADAMTS5 functions as an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. 2282 41