Procoagulant activity of the MC28 fibrosarcoma in vitro and in vivo : its role in metastasis
Procoagulant activity of the MC28 fibrosarcoma in vitro and in vivo : its role in metastasis
Patients with cancer have a high incidence of haemostatic activation and thrombotic complications possibly due to procoagulant activity (PCA) produced by malignant and activated host cells. Clotting activation also appears to be part of the pathology of metastatic tumour growth. Lung seeding in the MC28 fibrosarcoma model is reduced by warfarin suggesting that these cells interact with the haemostatic system. The present study was performed to determine the PCA of these cells in vitro, correlate this with their effects in vivo and to study mechanisms of the anti-metastatic action of warfarin in this model.
Viable MC28 cells strongly activated factor X (FX) in a chromogenic assay and shortened the recalcification time of whole blood, normal and FVII-deficient plasmas (P<0.001). PCA was strongly dependent on calcium and FVII, inhibited by Concanavalin (Con) A, phospholipase C and a polyclonal antibody to human tissue factor but unaffected by iodoacetamide and E-64. Intravenous injection of MC28 cells to hooded Lister rats reduced the platelet count (P<0.001) and factor X levels (P<0.05) and increased plasma haemoglobin (P<0.001). Electron microscopy showed platelet-associated fibrin deposition in the lung.
It is concluded that injection of MC28 cells causes intravascular coagulation as a direct result of a cellular tissue factor-FVIIa complex. The data suggest that the MC28 cells form a complex with platelets and fibrin which is retained in the pulmonary circulation (the organ of first encounter) long enough for some cells to extravasate and form lung tumours. Anticoagulation reduces tumour cell-platelet-fibrin complex formation, decreasing the time in the lung circulation and reducing seeding. These studies support the concept that haemostatic activation plays a role in metastasis and provides a biochemical basis for the anti-tumour effect of oral anticoagulants, at least in this animal model.
University of Southampton
Amirkhosravi, Mohammadali
060355d6-a816-40a5-a70f-5d55953905db
1993
Amirkhosravi, Mohammadali
060355d6-a816-40a5-a70f-5d55953905db
Amirkhosravi, Mohammadali
(1993)
Procoagulant activity of the MC28 fibrosarcoma in vitro and in vivo : its role in metastasis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Patients with cancer have a high incidence of haemostatic activation and thrombotic complications possibly due to procoagulant activity (PCA) produced by malignant and activated host cells. Clotting activation also appears to be part of the pathology of metastatic tumour growth. Lung seeding in the MC28 fibrosarcoma model is reduced by warfarin suggesting that these cells interact with the haemostatic system. The present study was performed to determine the PCA of these cells in vitro, correlate this with their effects in vivo and to study mechanisms of the anti-metastatic action of warfarin in this model.
Viable MC28 cells strongly activated factor X (FX) in a chromogenic assay and shortened the recalcification time of whole blood, normal and FVII-deficient plasmas (P<0.001). PCA was strongly dependent on calcium and FVII, inhibited by Concanavalin (Con) A, phospholipase C and a polyclonal antibody to human tissue factor but unaffected by iodoacetamide and E-64. Intravenous injection of MC28 cells to hooded Lister rats reduced the platelet count (P<0.001) and factor X levels (P<0.05) and increased plasma haemoglobin (P<0.001). Electron microscopy showed platelet-associated fibrin deposition in the lung.
It is concluded that injection of MC28 cells causes intravascular coagulation as a direct result of a cellular tissue factor-FVIIa complex. The data suggest that the MC28 cells form a complex with platelets and fibrin which is retained in the pulmonary circulation (the organ of first encounter) long enough for some cells to extravasate and form lung tumours. Anticoagulation reduces tumour cell-platelet-fibrin complex formation, decreasing the time in the lung circulation and reducing seeding. These studies support the concept that haemostatic activation plays a role in metastasis and provides a biochemical basis for the anti-tumour effect of oral anticoagulants, at least in this animal model.
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Published date: 1993
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Local EPrints ID: 462943
URI: http://eprints.soton.ac.uk/id/eprint/462943
PURE UUID: 40fa32ea-af99-4831-ac81-1e182c7e467c
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Date deposited: 04 Jul 2022 20:29
Last modified: 23 Jul 2022 01:08
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Author:
Mohammadali Amirkhosravi
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