Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders
Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders
复制标题
DOI：
10.1111/j.1582-4934.2008.00316.x
复制
发表时间：
2008-12-01
影响因子：
5.3
通讯作者：
Spek, C. Arnold
中科院分区：
文献类型：
--
作者：
Bruggemann, Lois W.;Versteeg, Henri H.;Spek, C. Arnold
实验动物研究和临床试验表明，针对凝血级联的干预措施可抑制癌细胞转移。这些数据支持这样的假设：先天性血栓前性疾病，如 V 因子 Leiden，促进转移，而出血性疾病，如血友病，则阻碍转移。为了检验这一假设，我们将因子 V Leiden 和因子 VIII 缺陷小鼠置于实验性肺转移的小鼠模型中。在此模型中，B16F10 小鼠黑色素瘤细胞被注射到尾静脉中，导致 20 天内出现多发性肺转移。与野生型同窝对照小鼠相比，半合子和纯合因子 VIII 缺陷小鼠均能免受肺转移。相比之下，纯合子 V 因子 Leiden 小鼠比野生型同窝小鼠出现更多的转移，而杂合子携带者则显示出中等数量的肺部病灶。总体而言，这些数据表明，对出血或血栓形成的先天易感性改变了血流中癌细胞的转移能力，并表明促凝血表型是肿瘤转移的危险因素。
Experimental animal studies as well as clinical trials have shown that interventions targeting the blood coagulation cascade inhibit cancer cell metastasis. These data support the hypothesis that congenital prothrombotic disorders, like factor V Leiden, facilitate metastasis whereas bleeding disorders, like haemophilia impede metastasis. To test this hypothesis, we subjected factor V Leiden and factor VIII deficient mice to a murine model of experimental lung metastasis. In this model, B16F10 murine melanoma cells are injected into the tail vein resulting in multiple lung metastases within 20 days. Both hemi- and homozygous factor VIII deficient mice were protected against lung metastasis compared to wild-type littermate controls. In contrast, homozygous factor V Leiden mice developed more metastases than wild-type littermates, whereas heterozygous carriers showed an intermediate number of pulmonary foci. Overall, these data show that a congenital susceptibility to either bleeding or thrombosis modifies the metastatic capacity of cancer cells in the bloodstream and suggest that procoagulant phenotypes are a risk factor for tumour metastasis.