Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human metalloelastase (MMP-12) has been implicated in elastin degradation and macrophage migration in many pathological conditions. It also generates angiostatin, thus having a potential to prevent tumour angiogenesis. It has previously been shown that transformed epithelial cells express MMP-12 in skin cancer. The aim of this study was further to elucidate the role of metalloelastase in squamous cell cancer (SCC) progression. By in situ hybridization, expression of MMP-12 mRNA was detected in 28/33 vulvar SCC samples in CD-68-positive macrophages, while 10 samples had positive cancer cells. By immunohistochemistry, MMP-12 protein was seen in the same area as the mRNA. MMP-12 mRNA expression in tumour cells correlated with more aggressive histology (p = 0.0099). In contrast, macrophage-derived MMP-12 mRNA was more abundant in well-differentiated grade I than grade III tumours (p = 0.01). However, the level of MMP-12 mRNA, regardless of its origin, did not correlate with metastasis or patient survival. No significant correlation was found between macrophage-derived MMP-12 mRNA and a low amount of blood vessels, as quantitated after von Willebrand staining. In agreement with vulvar SCCs in vivo, MMP-12 was expressed in cultured SCC cells by northern and western blot analysis. In HaCaTs and epithelial MCF-10f cells, MMP-12 mRNA was induced by transforming growth factor-beta1 (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) as measured by quantitative RT-PCR (TaqMan). Two MMPs capable of generating angiostatin in vivo, matrilysin (MMP-7) and gelatinase B (MMP-9), were also examined in these tumours. MMP-7 mRNA was mainly expressed by epithelial tumour cells, particularly in less differentiated tumours. MMP-9 was usually expressed by neutrophils and macrophages; epithelial protein was predominantly found in grade II/III tumours. These results suggest a dual role for MMP-12 in tumour progression.
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PMID:Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. 1223 87

Methanol and aqueous extracts of Styrax japonica Sieb. et Zucc used traditionally for the treatments of skin elastic materials were screened in vitro for the gelatinases B inhibitor actions. Erythrodiol-3-acetate (E) from the stem barks of S. japonica showed significant gelatinase B inhibition in human keratinocyte cells caused by ultraviolet irradiation. Here we investigated the effect of E, which was isolated from S. japonica on UV-induced premature skin aging. We studied the effect of E on UV-induced gelatinase B expression in an immortalized human keratinocyte cell line, in vitro. Acute UV irradiation induced gelatinase B expression at the protein levels and E suppressed this UV-induced gelatinase B expression in a dose-dependent manner. Taken together, these results show that E can prevent the harmful effects of UV that lead to skin aging or skin cancer. Therefore, we suggest that E should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging.
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PMID:WITHDRAWN: Erythrodiol-3-acetate isolated from Styrax japonica elicits the inhibition of UV-induced gelatinases B in cultured human keratinocyte cells. 1732 89

We previously revealed the crucial roles of a chemokine, CX3CL1, and its receptor, CX3CR1, in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1+ macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1+ tumor-associated macrophages with M2-like phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. In this mouse skin carcinogenesis process, CX3CR1+ tumor-associated macrophages exhibited M2-like phenotypes with the expression of Wnt3a and angiogenic molecules including VEGF and matrix metalloproteinase 9. Compared with wild-type mice, CX3CR1-deficient mice showed fewer numbers of skin tumors with a lower incidence. Concomitantly, M2-macrophage numbers and neovascularization were reduced with the depressed expression of angiogenic factors and Wnt3a. Thus, the CX3CL1-CX3CR1 axis can crucially contribute to skin carcinogenesis by regulating the accumulation and functions of tumor-associated macrophages. Thus, this axis can be a good target for preventing and/or treating skin cancers.
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PMID:Pivotal Involvement of the CX3CL1-CX3CR1 Axis for the Recruitment of M2 Tumor-Associated Macrophages in Skin Carcinogenesis. 3217 66