Differential Regulation of Platelet Aggregation by Matrix Metalloproteinases-9 and -2

Fernández-Patrón, Carlos; Martínez-Cuesta, María Ángeles; Salas, Eduardo; Sawicki, Grzegorz; Woźniak, Mieczysław; Radomski, Marek W.; Davidge, Sandra T.

doi:10.1055/s-0037-1614906

Cited by 175 publications

(183 citation statements)

References 25 publications

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“…Pearson r P-value R 2 0.2690 T1 T2 T3 T1 T2 T3 N1 N2 N0 N1 N2 0 I IIA IIB IIIA 0 I IIA IIB IIIA G1 G1-G2 G2-G3 G3 G2 G1 G1-G2 G2-G3 G3 G2 accelerators, since quiescent platelets release negligible amounts of gelatinases (Fernandez-Patron et al, 1999). On this ground, our major aim was to study the gelatinolytic levels of serum forms of MMP-2 and MMP-9 by zymographic assays, and correlate data with current clinicopathological parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Sera were obtained prior to surgery, according to the ethical standards, with informed consent of patients at the Maddalena Hospital. Native serum was prepared using plastic tubes without coagulation accelerators, to prevent the release of gelatinases during platelet activation (Fernandez-Patron et al, 1999). Tubes were centrifuged at 1600 g for 10 min, 30 min after blood collection.…”

Section: Sample Collectionmentioning

confidence: 99%

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Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

et al. 2004

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Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera (Po0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression (P ¼ 0.0273 for MMP-2 and P ¼ 0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression (P ¼ 0.0075 for MMP-2 and P ¼ 0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade (P ¼ 0.0511 for MMP-2 and P ¼ 0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.

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Section: Discussionmentioning

confidence: 99%

Section: Sample Collectionmentioning

confidence: 99%

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

et al. 2004

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“…Furthermore, MMP-9 exists in plasma as a monomer, complexed with neutrophil lipocalin and as a dimer, whereas MMP-2 is strictly monomeric. Despite their largely overlapping functions, MMP-2 and MMP-9 may even have opposing biological activity as illustrated by the finding that MMP-2 promotes platelet aggregation, but MMP-9 inhibits the same process (Fernandez-Patron et al, 1999).…”

Section: Gelatinases and Other Matrix Metalloproteinasesmentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

463

609

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“…The early studies led to the identification of many pro-and antiangiogenic factors that are stored in platelets and released after platelet activation. Among the angiogenesis promoters found in platelets are VEGF (16,17), platelet-derived growth factor (PDGF) (18), basic FGF (bFGF) (19), EGF (20), TGF (21), insulin-like growth factors (22), angiopoietin 1 (23), sphingosine-1-phosphate (24,25), and matrix metalloproteinases (26)(27)(28). The angiogenesis inhibitors found in platelets include thrombospondin I (29), platelet factor 4 (30), plasminogen activator inhibitor I (31), and angiostatin (32).…”

mentioning

confidence: 99%

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

Kisucka

Butterfield

Duda

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

323

241

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Platelets contain both pro-and antiangiogenic factors, but their regulatory role in angiogenesis is poorly understood. Although previous studies showed that platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis in vivo is largely uncharacterized. To address this topic, we used two in vivo approaches, the cornea micropocket assay and the Matrigel model, in four animal models: thrombocytopenic, Lyst bg (platelet storage pool deficiency), glycoprotein (GP) Ib␣͞IL4R transgenic (lacking extracellular GPIb␣, the receptor for von Willebrand factor as well as other adhesive and procoagulant proteins), and Fc␥R ؊/؊ (lacking functional GPVI, the collagen receptor) mice. Adult mice were rendered thrombocytopenic by i.p. administration of an antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice was lower in the cornea assay, and they showed significantly increased appearance of hemorrhage compared with mice treated with control IgG. The thrombocytopenic mice also showed more protein leakage and developed hematomas in the Matrigel model. GPIb␣͞IL4R transgenic mice presented increased hemorrhage in both assays, but it was less severe than in the platelet-depleted mice. Fc␥R ؊/؊ and Lyst bg mice showed no defect in experimental angiogenesis. Intravital microscopy revealed a >3-fold increase in platelet adhesion to angiogenic vessels of Matrigel compared with mature quiescent skin vessels. Our results suggest that the presence of platelets not only stimulates angiogenic vessel growth but also plays a critical role in preventing hemorrhage from the angiogenic vessels. The adhesion function of platelets, as mediated by GPIb␣, significantly contributes to the process. thrombocytopenic mice ͉ blood vessel ͉ ␣-granule ͉ cornea ͉ collagen receptor

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Differential Regulation of Platelet Aggregation by Matrix Metalloproteinases-9 and -2

Cited by 175 publications

References 25 publications

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera

Gelatinase-mediated migration and invasion of cancer cells

Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage

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