Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.
Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
Amirkhosravi
M
M
Hemostasis and Thrombosis Research Unit, Walt Disney Memorial Cancer Institute at Florida Hospital, Altamonte Springs 32701, USA.
Francis
J L
JL
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D005337:Fibrin / Q000032:analysis; D005354:Fibrosarcoma / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control / Q000556:secondary*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D007275:Injections, Intravenous; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control / Q000556:secondary*; D008262:Macrophage Activation; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use
D016895:Culture Media, Serum-Free; D009363:Neoplasm Proteins; D003208:Concanavalin A; D014859:Warfarin; D005337:Fibrin; D006493:Heparin; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant