THE EFFECT OF WARFARIN AND FACTOR-VII ON TISSUE PROCOAGULANT ACTIVITY AND PULMONARY SEEDING
THE EFFECT OF WARFARIN AND FACTOR-VII ON TISSUE PROCOAGULANT ACTIVITY AND PULMONARY SEEDING
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DOI：
10.1038/bjc.1992.67
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发表时间：
1992-03-01
影响因子：
8.8
通讯作者：
TAYLOR, I
中科院分区：
文献类型：
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作者：
FRANCIS, JL;CARTY, N;TAYLOR, I
肿瘤周围纤维蛋白是肿瘤基质的一致特征，并且在肿瘤细胞接种后不久沉积。 由于纤维蛋白可能通过多种方式有益于肿瘤生长，因此正常或恶性组织产生纤维蛋白的能力可能会影响转移。 许多正常组织和肿瘤细胞由于组织因子和因子 VII 的复合物而具有促凝血活性。 我们测量了正常大鼠、使用华法林稳定的大鼠以及注射了因子 VII 的类似抗凝动物的这种组织促凝血活性。 还评估了注射 MC28 纤维肉瘤细胞后华法林和因子 VII 对肺部播散的影响。 华法林显着降低肾上腺、肺和结肠的促凝血活性（P < 0.001）。 施用因子VII显着增加抗凝大鼠的肺和肾上腺组织促凝血活性（P < 0.02）。 与对照动物相比，华法林处理的大鼠原发肿瘤生长明显减慢（P < 0.001），肺沉积物更少（P < 0.001）。 注射因子 VII 可将肺部播散恢复至对照水平（P < 0.001）。 华法林在体外不会影响细胞的粘附能力，也不会减少静脉注射后物理滞留在肺部的肿瘤细胞数量。 结论是，正常组织的促凝血活性可能影响其支持肿瘤生长的能力，并且华法林的抗转移作用可能至少部分归因于该活性所需的因子VII的可用性的减少。
Peri-tumour fibrin is a consistent feature of tumour stroma and is deposited shortly after tumour cell inoculation. Since there are several ways in which fibrin may be beneficial to tumour growth, it is possible that the ability of normal or malignant tissue to generate fibrin may influence metastasis. Many normal tissues and tumour cells possess a procoagulant activity that is due to a complex of tissue factor and factor VII. We have measured this tissue procoagulant activity in normal rats, rats stabilised on Warfarin and similarly anticoagulated animals injected with factor VII. The effect of Warfarin and factor VII administration on pulmonary seeding following injection of MC28 fibrosarcoma cells was also assessed. Procoagulant activity in adrenal, lung and colon was significantly reduced by Warfarin (P < 0.001). Administration of factor VII significantly increased lung and adrenal tissue procoagulant activity in anticoagulated rats (P < 0.02). Warfarinised rats had significantly slower primary tumour growth (P < 0.001) and fewer lung deposits than control animals (P < 0.001). Injection of factor VII restored pulmonary seeding to control levels (P < 0.001). Warfarin did not affect the ability of the cells to adhere in vitro and did not reduce the number of tumour cells physically trapped in the lungs after intravenous injection. It is concluded that the procoagulant activity of normal tissues may influence their ability to support tumour growth and that the antimetastatic effect of Warfarin may be at least partly due to a reduction in the availability of the factor VII required for this activity.