Role of von Willebrand factor in tumour cell‐induced platelet aggregation: differential regulation by NO and prostacyclin

Jurasz, Paul; Stewart, Michael W.; Radomski, Anna; Khadour, Fadi; Duszyk, Marek; Radomski, Marek W.

doi:10.1038/sj.bjp.0704343

Cited by 39 publications

(48 citation statements)

References 45 publications

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“…17,23 Briefly, to analyze SELP expression, platelet aggregation was terminated at 30% maximal response, as determined using an aggregometer, in platelet exposed to different SiNP (10SiNP, 50SiNP, 150SiNP, and 500SiNP) at different concentrations (1 to 200 µg/mL). Platelet suspensions and anti-selectin-P antibody (BD) were then mixed and incubated in the dark at room temperature for 5 minutes.…”

Section: Selectin P and Gpiib/iiia Analyses By Flow Cytometrymentioning

confidence: 99%

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Corbalan

Medina

Jacoby³

et al. 2012

IJN

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Methods: Nanoparticle-platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO -released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy. Results: Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO -leading to an unfavorably low [NO]/[ONOO -] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size. Conclusions: The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO -] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets.

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Section: Selectin P and Gpiib/iiia Analyses By Flow Cytometrymentioning

confidence: 99%

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Corbalan

Medina

Jacoby³

et al. 2012

IJN

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“…Cells were detached from the flasks using EDTA (ethylenediaminetetraacetic acid) (7 mM) in DMEM with 10% FBS and gentle shaking as previously described. 15,35,36 EDTA was then washed away with Tyrode solution, and the cells were resuspended in Tyrode solution at a concentration of 10 6 /mL.The HUV-EC-C cell line was cultured as monolayers in 75-cm 2 culture flasks at 37°C in a humidified atmosphere with 5% CO 2 . The cells were cultured in 90% Kaighn F12K medium with gentamicin (0.05 mg/mL), penicillin (0.06 mg/mL), streptomycin (0.01 mg/mL), and 10% FBS.…”

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confidence: 99%

“…Platelet aggregation was then initiated by the addition of collagen (5 g/mL), thrombin (0.1 U/mL), or HT-1080 cells (1 ϫ 10 4 /mL) and monitored by Aggro-Link software for 15 minutes as previously described. 15,35,36 After aggregation, platelet pellets were separated from releasates using centrifugation (1800g for 10 minutes) and then stored at Ϫ80°C until assayed for the presence of angiostatin by Western blot analysis. …”

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confidence: 99%

Generation and role of angiostatin in human platelets

Jurasz

Alonso

Castro-Blanco

et al. 2003

Blood

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Platelets regulate new blood vessel growth, because they contain a number of angiogenesis promoters and inhibitors. Additionally, platelets contain matrix metalloproteinases (MMPs), which when released mediate platelet adhesion and aggregation, and plasminogen, a fibrinolytic system enzyme that serves to limit blood clot formation. Enzymatic cleavage of plasminogen by MMPs generates angiostatin, an angiogenesis inhibitor. Therefore, we examined whether platelets generate angiostatin during aggregation in vitro. Platelets were isolated from healthy human donors and then aggregated with collagen, thrombin, or HT-1080 fibrosarcoma cells. Angiostatin was detected by Western blot analysis in the platelet releasates of all blood donors irrespective of the aggregating agent used. Platelet pellet homogenates showed the presence of angiostatin in all donors, which was released upon aggregation. Furthermore, platelet-derived angiostatin was isolated and purified by lysine-Sepharose affinity chromatography from collagen-aggregated platelet releasates. Bioassay of platelet-derived angiostatin showed that it inhibited the formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in an in vitro angiogenesis model. Inhibition of angiostatin in platelet releasates promoted the formation of capillary structures by HUV-EC-Cs. We conclude that healthy human platelets contain angiostatin, which is released in active form during platelet aggregation, and platelet-derived angiostatin has the capacity to inhibit angiogenesis. IntroductionPlatelets play a vital role in maintaining hemostasis by forming white aggregates that seal breaches in vascular integrity. In addition to preventing bleeding, platelets are known to play roles in nonhemostatic processes such as immunity 1 and regulation of angiogenesis. 2 Platelets contain a number of proangiogenic and antiangiogenic factors, which have the potential to regulate angiogenesis. Among the angiogenesis promoters found in platelets are vascular endothelial growth factor (VEGF)-A 3 and -C, 4 platelet-derived growth factor (PDGF), 5 basic fibroblastic growth factor (bFGF), 6 and epidermal growth factor (EGF). 7 Furthermore, platelets contain matrix metalloproteinases (MMPs), [8][9][10] which are also known to promote angiogenesis, 11 and often are used as markers of the angiogenic process. To balance off the effects of the angiogenesis promoters, a number of angiogenesis inhibitors are also found in platelets. Included among this group are thrombospondin (TSP-1), 12 platelet factor 4 (PF4), 13 transforming growth factor-␤1 (TGF-␤1), 14 19,20,20, In addition to MMPs, a number of other proteases have been shown to generate angiostatin, including urokinase (uPA) and tissue-type plasminogen activator (tPA). 23 The generation of angiostatin has been found primarily in tumor cells, 24-27 although macrophages have also been shown to form angiostatin as a byproduct of the proteolytic regulation of membrane-bound plasmin. 28 Interestingly, platelets have the ability to...

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“…We have previously demonstrated the role of MMP-2 and MT1-MMP in tumor cell-induced platelet aggregation and showed reciprocal interactions between platelets and tumor cells (Jurasz et al, 2001a;Alonso-Escolano et al, 2004). These reciprocal interactions result, among others, in profound changes in the surface expression of glycoprotein receptors, both in platelets and tumor cells (Jurasz et al, 2001b;Alonso-Escolano et al, 2004). These findings prompted us to study the significance of tumor cell-platelet interactions in the next step of metastasis, which involves the degradation or remodeling of the basement membrane for the tumor cell extravasation.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase Cδ Mediates Platelet-Induced Breast Cancer Cell Invasion

Alonso-Escolano

Medina

Cieslik

et al. 2006

J Pharmacol Exp Ther

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Platelets play an important role in carcinogenesis, but the underlying molecular mechanisms remain poorly understood. To investigate the effects of platelets on in vitro invasion of MCF7 human breast cancer cells, human MCF7 cells were used to study their interactions with platelets using aggregometry and cell invasion chambers. Zymography and quantitative polymerase chain reaction (PCR) were used to study matrix metalloproteinases (MMPs), whereas Western blot was used to study protein kinase C (PKC) ␦ in MCF7 cells. We observed that platelets promoted invasion of MCF7 cells (3-fold increase, p Ͻ 0.05, n ϭ 3) and that this process correlated with a dramatic increase in MMP-9 (8 fold-increase, p Ͻ 0.001, n ϭ 3), which is known to facilitate cancer cell invasion. Because both platelets and MCF7 cells have been shown to release MMP-9, we investigated the cellular source that accounted for this increase. The time course and the use of specific protein synthesis inhibitors demonstrated that most of the increase in MMP-9 levels derived from de novo synthesis of this protease by cancer cells.

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Role of von Willebrand factor in tumour cell‐induced platelet aggregation: differential regulation by NO and prostacyclin

Cited by 39 publications

References 45 publications

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Generation and role of angiostatin in human platelets

Protein Kinase Cδ Mediates Platelet-Induced Breast Cancer Cell Invasion

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