Isolation of Fibrinogen–Fibrin Related Antigen from Human Plasma by Immunoaffinity Chromatography: its Characterization in Normal Subjects and in Defibrinating Patients with Abruptio Placentae and Disseminated Cancer

Merskey, Clarence; Johnson, Alan J.; Harris, Joel U.; Wang, M. T.; Swain, Sandra M.

doi:10.1111/j.1365-2141.1980.tb08720.x

Cited by 42 publications

(17 citation statements)

References 40 publications

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“…Indeed, there is abundant evidence that many tumor cells activate the coagulation system with generation of thrombin (37). Low-grade intravascular coagulation as diagnosed by increased fibrinogen turnover (38) increased plasma levels of fibrinogen/fibrin-related antigen (38) and increased plasma levels of fibrinopeptide A has been observed in most patients with solid tumors (39)(40)(41). One study noted elevated fibrinopeptide-A levels in 60% of patients at time of presentation with increasing levels noted with progression of disease.…”

Section: Discussionmentioning

confidence: 99%

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Nierodzik¹,

Plotkin²,

Kajumo³

et al. 1991

J. Clin. Invest.

232

157

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Recent studies have revealed a role for platelets and the platelet-adhesive proteins, fibronectin and von Willebrand factor (vWF) in platelet-tumor cell interaction in vitro and metastasis in vivo. The present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo. In vitro, thrombin at 100-1,000 mU/ml maximally stimulated the adhesion of six different tumor cell lines from three different species two-to fivefold. As little as 1-10 mU/ml was effective. The effect of thrombin was specific (inhibitable by hirudin, dansyl-arginine N43-ethyl-1,5 pentanediyl) amide and unreactive with the inactive thrombin analogue N-P-tosyl-L-phenylchloromethylketone-thrombin and D-phenylalanyl-L-propyl-L-arginine chloromethylketone-thrombin (PPACK-thrombin), and required high-affinity thrombin receptors (competition with PPACK-thrombin but not with N-P-tosyl-L-lysine-chloromethyl-ketone-thrombin). Functionally active thrombin was required on the platelet surface. Binding of tumor cells to thrombin-activated platelets was inhibitable by agents known to interfere with the platelet GPIIb-GPIIIa integrin: monoclonal antibody 10E5, tetrapeptide RGDS and 'y chain fibrinogen decapeptide LGGAKQAGDV, as well as polyclonal antibodies against the platelet adhesive ligands, fibronectin and vWF. In vivo, thrombin at 250-500 mU per animal increased murine pulmonary metastases fourfold with CT26 colon carcinoma cells and 68-413-fold with B16 amelanotic melanoma cells. Thus, thrombin amplifies tumor-platelet adhesion in vitro twoto fivefold via occupancy of high-affinity platelet thrombin receptors, and modulation of GPIIb-GPIIIa adhesion via an RGD-dependent mechanism. In vivo, thrombin enhances tumor metastases 4-413-fold with two different tumor cells lines. (J. Clin. Invest. 1991. 87:229-236.).

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Section: Discussionmentioning

confidence: 99%

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Nierodzik¹,

Plotkin²,

Kajumo³

et al. 1991

J. Clin. Invest.

232

157

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“…50 Up-regulation of both VEGF and Ang-2 by thrombin indicates that angiogenesis might be facilitated by thrombosis. Thus, the well-described association of thrombosis with cancer [16][17][18][19][20] may be contributing to tumorigenesis by the initiation of thrombin-stimulated angiogenesis, which could explain, at least in part, the enhancement of experimental tumorigenesis by thrombin. [21][22][23][24][25] BLOOD, 1 MARCH 2002 ⅐ VOLUME 99, NUMBER 5 For personal use only.…”

Section: Discussionmentioning

confidence: 99%

“…16 Many studies have described a systemic activation of the blood coagulation cascade in patients with cancer. [17][18][19][20] Recent studies have shown that thrombin-treated tumor cells have an increased ability to adhere to von Willebrand factor, fibronectin, platelets, and endothelial cells and form pulmonary metastases in syngeneic mice. [21][22][23][24][25] However, the data do not define the mechanism by which thrombin promotes tumor progression and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells

Huang

et al. 2002

Blood

124

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Angiogenesis is required for tumor growth and metastasis. It has recently been suggested that thrombin is a potent promoter of angiogenesis. We therefore examined the possibility that thrombin could be inducing the expression of angiopoietin-2 (Ang-2), necessary for remodeling. Human umbilical vein endothelial cells were incubated with or without thrombin (1 U/mL) for 1 to 24 hours and then examined for messenger RNA (mRNA) by Northern analysis. Enhanced mRNA expression (about 4-fold over baseline) was noted at 4 hours. Enhanced expression of Ang-2 mRNA was secondary to enhanced transcription (about 4-fold), with no effect on stabilization. Enhanced Ang-2 mRNA transcription was inhibited by H7 and PD98059, indicating the requirement of serine/threonine kinases as well as the mitogen-activated protein kinase pathway.

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“…35 The binding of thrombin36,37 and factor X11I38 to fibrin may explain the increase in thrombin-catalyzed factor XIIIa by fibrin polymers in plasma.10 Prior studies provided indirect evidence for circulating crosslinked fibrin polymers by identifying y chain dimers in extracts of plasma obtained from patients with thrombotic disease. [15][16][17][18][19]39 Using an electrophoretic technique, we have shown directly a low concentration of crosslinked fibrin dimer in normal plasma and a significant elevation in patients with acute myocardial infarction. 7 Tissue plasminogen activator has a high affinity for fibrin29,30 and preferentially activates fibrinbound plasminogen,4041 which are properties that localize physiologic fibrinolysis and that also form the theoretical basis for the relative fibrin selectivity of t-PA as a therapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

et al. 1989

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After addition of a low concentration of thrombin to normal plasma, a progressive and significant increase in crosslinked fibrin polymers was found by sodium dodecyl sulfate agarose gel electrophoresis, reaching 27% of total fibrinogen and fibrin before gel formation. As measured by enzyme-linked immunosorbent assay with a monoclonal antibody specific for an epitope near the yy crosslink site, increased immunoreactivity of plasma did not occur after adding thrombin despite formation of crosslinked fibrin polymers, which indicates that the antibody does not recognize the epitope in the polymers. Addition of tissue-type plasminogen activator (t-PA) to plasma resulted in a more rapid degradation of fibrin polymers than of fibrinogen, indicating that the fibrin specificity of t-PA is retained with soluble fibrin. Coincident with degradation of plasma crosslinked fibrin polymers, plasma DD immunoreactivity increased 70-fold from 50.3±4.5 (mean±SD) to 3,560±1,235 ng/ml. The presence of increased crosslinked fibrin polymers produced by adding thrombin to plasma significantly increased maximum immunoreactivity after t-PA-induced degradation to 18,500±11,780 ng/ ml. The increase in DD immunoreactivity was dependent on t-PA concentration; no elevation occurred below 0.01 ug/ml, and maximal increases occurred above 100 ,ug/ml. Analysis of gel electrophoretic patterns of thrombin and t-PA-treated plasma samples suggests that the DD reactivity of t-PA-treated plasma is mainly due to degradation of soluble crosslinked fibrin polymers. Our findings indicate that plasmic degradation of soluble fibrin polymers in plasma may be an important source of fragment DD during thrombolytic therapy. (Circulation 1989;79: 666-673) U nder physiologic conditions, fibrin formation is localized either intravascularly in the formation of hemostatic plugs or extravascularly in inflammatory foci. However, low concentrations of soluble fibrin circulate, and increased concentrations have been identified in patients with thrombotic disease,1-7 reflecting a systemic effect of thrombin activity that can also be measured by plasma fibrinopeptide levels.8,9 Solu-

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Isolation of Fibrinogen–Fibrin Related Antigen from Human Plasma by Immunoaffinity Chromatography: its Characterization in Normal Subjects and in Defibrinating Patients with Abruptio Placentae and Disseminated Cancer

Cited by 42 publications

References 40 publications

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo.

Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells

Increased immunoreactivity of plasma after fibrinolytic activation in an anti-DD ELISA system. Role of soluble crosslinked fibrin polymers.

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