Evidence that cells from experimental tumours can activate coagulation factor X

Abstract

Summary.-The procoagulant activity of cells from some experimental tumours isolated in culture or in single-cell suspensions from ascitic fluid was investigated. 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 but not of Factor X-deficient human plasma. The same cells generated thrombin when mixed with a source of prothrombin and Factor X, absorbed bovine serum (as a source of Factor V), phospholipid and calcium chloride. Thrombin formation was not influenced by the presence of Factor VII. Cells from Sarcoma 180 ascites were completely inactive in both test systems. It is concluded that cells from some experimental tumours have the capacity to activate Coagulation Factor X directly. These findings suggest the existence of an alternative "cellular" pathway in the initiation of blood clotting distinct from both the intrinsic and extrinsic mechanisms.

Role of thrombin as a tumor growth factor

“…Indeed, there is abundant evidence that many tumor cells have constitutively active tissue factor on their surface which can activate the coagulation system with generation of thrombin. [24][25][26][27][28][29][30] Indeed, low-grade intravascular coagulation as diagnosed by increased fibrinogen turnover, 31 increased plasma levels of fibrinogen/fibrin-related antigen 31 and increased plasma levels of fibrinopeptide A have been observed in most patients with solid tumors. [32][33][34] One study noted elevated fibrinopeptide-A levels in 60% of cancer patients at time of disease.…”

A factor X-activating cysteine protease from malignant tissue.

“…A proteolytic enzyme, cancer procoagulant, has been purified from rabbit V2 carcinoma and some of its physical, chemical, and enzymatic properties have been determined.' In addition, cancer procoagulant activity has been identified in extracts of several human malignant tumors (9) and in cultured malignant cells2 (10)(11)(12)(13) Citrated bovine and human plasma were obtained fresh and prepared as described previously (14) for use in the singlestage recalcified coagulation time assay. Pure bovine Factor X was kindly provided by Dr. Earl Davie and used in the twostage clotting assay as described previously (14).…”

Platelet Contribution to the Formation of Metastatic Foci: The Role of Cancer Cell-Induced Platelet Activation

“…It is also impor tant to point out that these variations may be ascribed to the use of heterologous systems since a species difference has been noted in platelet aggregation induced by tumor cells [9]. The mechanisms that have been pro posed include: ( 1 ) generation of thrombin by tumor activation of the clotting factors [10][11][12], (2) activation by ADP [7,13], (3) release of cathepsin B [14], activation of the arachidonate metabolism [15,16] or a combina tion of these mechanisms.…”