Matrix Metalloproteinases and Their Inhibitors

Kugler, A.; Thelen, Paul; Ringert, Rolf-Hermann

doi:10.1385/1-59259-144-2:139

Cited by 56 publications

(52 citation statements)

References 9 publications

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“…TIMP3 (tissue inhibitor of metaloproteinase number 3) inhibits the matrix metaloproteinases MMPs. Excess of MMPs stimulates tumour invasion and metastasis (Kugler, 1999;Sato et al, 1992). Cyclin D1 initiates the G1-S phase progression (Chen et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

et al. 2000

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SummaryThe recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in geneexpression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

et al. 2000

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“…Matrix metalloproteinases (MMPs) are a family of zinc-catalyzed proteolytic enzymes known to digest the basement membrane, ECM components, and cell surface proteins [1]. MMPs have been linked with cancer cell invasion, growth, angiogenesis, inflammation, and metastasis [1][2][3][4][5]. In addition, MMPs have been shown to play a role in the release of growth factors that can in turn contribute to the invasiveness and growth of tumors [6].…”

Section: Introductionmentioning

confidence: 99%

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

et al. 2006

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The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 (MMP-26) promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p<0.0001) MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer (p<0.001 for each) in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

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“…Heparin, chemically modified heparins and related sulphated polysaccharides are known to be effective inhibitors for heparanase (Irimura et al, 1986;Vlodavsky et al, 1994;Lapierre et al, 1996) and various matrix metalloproteases (MMPs) including MMP-1, -2, -3 and -9 (Kenagy et al, 1994;Gogly et al, 1998). MMP-2 and -9 are suggested to play a major role in metastasis (Kugler, 1999;Westermarck and Kahari, 1999). Heparanase activity has also been found to correlate with the metastatic potential of various types of cancer cells (Nakajima et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

et al. 2002

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Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant heparin-carrying polystyrene on tumour growth and metastasis. Non-anticoagulant heparin-carrying polystyrene has a higher activity to inhibit vascular endothelial growth factor-165-, fibroblast growth factor-2-or hepatocyte growth factor-induced human microvascular endothelial cell growth than heparin, ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin, which is probably due to the heparin-clustering effect of non-anticoagulant heparin-carrying polystyrene. Non-anticoagulant heparin-carrying polystyrene inhibited human microvascular endothelial cell, B16 melanoma and Lewis lung cancer cell adhesion to Matrigel-coated plates. Non-anticoagulant heparin-carrying polystyrene also showed strong inhibitory activities in the tubular formation of endothelial cells on Matrigel and B16-melanoma and Lewis lung cancer cell invasion in a Matrigel-coated chamber assay. In vivo studies showed that growth of subcutaneous induced tumours and lung metastasis of B16-melanoma and Lewis lung cancer cells were more effectively inhibited by non-anticoagulant heparin-carrying polystyrene than ten periodate-oxidized-heparin and ten periodate-oxidized-low molecular weight-heparin. Furthermore, non-anticoagulant heparin-carrying polystyrene markedly reduced the number of CD34-positive vessels in subcutaneous Lewis lung cancer tumours, indicating a strong inhibition of angiogenesis. These results suggest that non-anticoagulant heparin-carrying polystyrene has an inhibitory activity on angiogenesis and tumour invasion and may be very useful in cancer therapy.

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Matrix Metalloproteinases and Their Inhibitors

Cited by 56 publications

References 9 publications

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

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