Several murine metastasizing tumors possess a cysteine proteinase with cancer procoagulant characteristics

Abstract

Cancer Procoagulant (CP), a cysteine proteinase which triggers blood coagulation by directly activating Factor X (FX) in the absence of Factor VII (F VII), has recently been isolated from rabbit V2 carcinoma and biochemically characterized. We have studied the procoagulant activity of tissue extracts from 4 murine experimental tumors in order to define whether or not a F VII-independent activity with cysteine proteinase characteristics was present. The tumors studied were: Lewis lung carcinoma (3LL), B16 melanoma (B16), JW sarcoma (JWS) and the M4 variant of the mFS6 fibrosarcoma (M4). Extracts from 3LL, B16 and JWS tumor initiated coagulation in both the presence and absence of F VII, their procoagulant activity was sensitive to iodoacetamide (1 mM) and mercury chloride (0.1 mM). The procoagulant of M4 extract was dependent on the presence of F VII and was not significantly affected by the cysteine proteinase inhibitors. An Ouchterlony double immunodiffusion study showed immunological cross-reactivity of all but M4 extracts to a polyclonal antibody to purified CP. The present study suggests that the procoagulant(s) present in the murine tumors 3LL, B16 and JWS are enzymatically and immunologically indistinguishable from cancer procoagulant of the rabbit V2 carcinoma.

Pathogenetic Mechanisms of Thrombosis in Malignancy

“…Tumor cells may express different types of procoagulant activities [29]; besides the already mentioned TF, which is constitutively expressed by most tumor and leukemia cells [30], CP, a cysteine protease with direct factor X activating activity, is expressed by some experimental and human tumor cells [16, 20, 31, 32, 33, 34, 35]. It is confined to the malignant phenotype and, in murine tumors, it is associated with the metastatic potential of tumor cells.…”

Cancer and Thrombosis

“…Cancer cells, indeed, are able to interact with platelets, clotting and fibrinolytic systems as well as with endo thelial cells. Emphasis has been given to the role of tumor procoagulants in blood clot ting activation associated with tumor and metastasis growth [11], Tumor cells may express diferent types of procoagulant activities: besides tissue thromboplastin, which is expressed constitutively by most tumor and leukemia cells, «cancer procoagulant» (CP), a cysteine protease with direct factor X activating acti vity, is expressed by some experimental and human tumor cells [12][13][14]. It is confined to the m alignant phenotype and, in murine tumors, it is associated with the metastatic potential of tumor cells [14].…”

“…Emphasis has been given to the role of tumor procoagulants in blood clot ting activation associated with tumor and metastasis growth [11], Tumor cells may express diferent types of procoagulant activities: besides tissue thromboplastin, which is expressed constitutively by most tumor and leukemia cells, «cancer procoagulant» (CP), a cysteine protease with direct factor X activating acti vity, is expressed by some experimental and human tumor cells [12][13][14]. It is confined to the m alignant phenotype and, in murine tumors, it is associated with the metastatic potential of tumor cells [14]. Experiments with warfarin and vitamin K deficient diet suggest CP is a novel vitamin K dependent activity [12]: this is also true for human malignant cells (such as melanoma or colon carcinoma cells) as indicated by experiments in nude mice [15].…”

Vascular attack as a therapeutic strategy for cancer

“…1990). Detailed studies have indicated that the coagulation cascade is modulated by endothelialderived factors, and that the presence of a tumour can tip the balance towards a pro-coagulant state (Falanga et al 1987;Murray et al 1989;Zacharski et al 1987;Stern et al 1985;Murray et aL 1990) by modifying endothelial activity. Evidence is accumulating that this balance can be further tipped by the addition of TNF or FAA to the system, either in vitro or in vivo Clauss et al 1990).…”