Amirkhosravi M, Francis J L
Hemostasis and Thrombosis Research Unit, Walt Disney Memorial Cancer Institute at Florida Hospital, Altamonte Springs 32701, USA.
Thromb Haemost. 1995 Jan;73(1):59-65.
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)
肿瘤细胞以多种方式与止血系统相互作用，从而可能影响恶性肿瘤的生长和扩散。MC28纤维肉瘤细胞具有强大的促凝活性（PCA），静脉注射后可形成肺肿瘤。本研究的目的是探讨MC28模型中PCA、血管内凝血与肺种植之间的关系。将MC28细胞注入对照、华法林化和肝素化的带帽利斯特大鼠体内。通过血栓弹力图（TEG）和Sonoclot分析（SA）监测凝血变化，通过光镜和电镜观察肺纤维蛋白形成，通过宏观计数观察肿瘤种植，通过放射性标记观察肺内肿瘤细胞和血小板沉积。通过发色底物法测定PCA。MC28的PCA被鉴定为一种组织因子-因子VIIa复合物，可能在细胞培养或实体瘤解聚过程中产生。注射肿瘤细胞导致明显的凝血病，并迅速（30分钟内）继发肺内纤维蛋白沉积和放射性标记血小板的积聚。肝素和华法林显著减少肺种植（p<0.001），并减少放射性标记肿瘤细胞在肺循环中的滞留（p<0.01）。用伴刀豆球蛋白A预先处理抑制细胞PCA可显著减少血管内凝血和肺种植。我们得出结论，MC28细胞因其促凝活性直接导致血管内凝血。数据表明，肿瘤细胞与血小板和纤维蛋白形成复合物，这些复合物在肺内保留足够长的时间，以便发生外渗和种植。（摘要截短至250字）
