Evidence that cells from experimental tumours can activate coagulation factor X

Although available information indicates that cancer cells may activate blood coagulation, the precise mechanism remains still uncertain. A procoagulant with characteristics of tissue thromboplastin has been found in human benign and malignant tissues and in some experimental tumors. On the other hand it has been reported that extracts from malignant tissues directly activate coagulation factor X, due to the presence of a serine protease. We have investigated the procoagulscitic fluid. Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, factor VIII and factor VII-deficient, not of factor X-deficient human plasma. The same cells did generate thrombin when mixed with a source of prothrombin and factor X, absorbed bovine serum (as a source of factor V), phospholipid and CaCl2.Cells from Sarcoma ISO ascites were completely inactive in both test systems. It was a included that cells from some experimental tumors, similarly to normal platelets, possess the capacity to directly activate coagulation factor X. This suggests the existence of an alternative “cellular” pathway in blood clotting initiation distinct from both the intrin sic and extrinsic mechanisms.(Supported by Italian CNR and NIH, NCI, USA).

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Immunological Studies on the Blood Coagulation Factor X and Its Warfarin-induced Precursor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649144 ◽

1974 ◽

Vol 31 (01) ◽

pp. 040-051 ◽

Cited By ~ 5

Author(s):

Gustav Gaudernack ◽

Åse Gladhaug Berre ◽

Bjarne Østerud ◽

Hans Prydz

Keyword(s):

Coagulation Factor ◽

Factor X ◽

Intrinsic Pathway ◽

Coagulation Activity ◽

Factor X Deficiency ◽

Warfarin Treatment ◽

The Cross ◽

Monospecific Antisera ◽

Purified Antigen ◽

Congenital Factor

SummaryMonospecific antisera against the human coagulation factor X have been raised in rabbits by injections of purified antigen. Such antiserum was used to study the cross-reacting material without factor X activity which is present in the blood of warfarin-treated patients and animals as well as to study the changes in factor X during coagulation. One patient with congenital factor X deficiency was also studied.A complete identity was found between factor X in Macaca mulatta and human blood. During warfarin treatment antigenically cross-reacting material appeared in plasma. This was not adsorbed on BaSO4, and inhibited the coagulation activity of normal factor X.Both this material, normal factor X and the cross-reacting material in plasma from a patient congenitally deficient in factor X gave rise to split products during coagulation by the intrinsic pathway, i. e. all of them served as substrates for the intrinsic activator of factor X.

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Characterization of Recombinant Human Coagulation Factor XFriuli

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650267 ◽

1996 ◽

Vol 75 (02) ◽

pp. 313-317 ◽

Cited By ~ 8

Author(s):

D J Kim ◽

A Girolami ◽

H L James

Keyword(s):

Catalytic Domain ◽

Coagulation Factor ◽

Molecular Size ◽

Binding Pocket ◽

Site Directed Mutagenesis ◽

Bleeding Tendency ◽

Factor X ◽

Amino Terminal ◽

Normal Plasma ◽

Plasma Factor

SummaryNaturally occurring plasma factor XFriuli (pFXFr) is marginally activated by both the extrinsic and intrinsic coagulation pathways and has impaired catalytic potential. These studies were initiated to obtain confirmation that this molecule is multi-functionally defective due to the substitution of Ser for Pro at position 343 in the catalytic domain. By the Nelson-Long site-directed mutagenesis procedure a construct of cDNA in pRc/CMV was derived for recombinant factor XFriuli (rFXFr) produced in human embryonic (293) kidney cells. The rFXFr was purified and shown to have a molecular size identical to that of normal plasma factor X (pFX) by gel electrophoretic, and amino-terminal sequencing revealed normal processing cleavages. Using recombinant normal plasma factor X (rFXN) as a reference, the post-translational y-carboxy-glutamic acid (Gla) and (β-hydroxy aspartic acid (β-OH-Asp) content of rFXFr was over 85% and close to 100%, respectively, of expected levels. The specific activities of rFXFr in activation and catalytic assays were the same as those of pFXFr. Molecular modeling suggested the involvement of a new H-bond between the side-chains of Ser-343 and Thr-318 as they occur in anti-parallel (3-pleated sheets near the substrate-binding pocket of pFXFr. These results support the conclusion that the observed mutation in pFXFr is responsible for its dysfunctional activation and catalytic potentials, and that it accounts for the moderate bleeding tendency in the homozygous individuals who possess this variant procoagulant.

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Activation of Human Coagulation Factor VIII by Activated Factor X, the Common Product of the Intrinsic and the Extrinsic Pathway of Blood Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657137 ◽

1982 ◽

Vol 47 (02) ◽

pp. 096-100 ◽

Cited By ~ 22

Author(s):

K Mertens ◽

R M Bertina

Keyword(s):

Factor Viii ◽

Human Factor ◽

Intrinsic Factor ◽

Factor Xa ◽

Coagulation Factor ◽

Factor X ◽

Extrinsic Factor ◽

Extrinsic Pathway ◽

Factor Ixa ◽

The Common

SummaryThe intrinsic activation of human factor X has been studied in a system consisting of purified factors and in plasma. In both these systems factor Xa stimulated the activation of factor X by factor IXa plus factor VIII This is due to the activation of factor VIII by factor Xa. When this factor Xa is formed via the extrinsic pathway, the extrinsic factor X activator functions as a stimulator of the intrinsic factor X activator.

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