Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice
Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice
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DOI：
10.1038/sj.onc.1201869
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发表时间：
1998-06-18
期刊：
影响因子：
8
通讯作者：
Degen, JL
中科院分区：
文献类型：
--
作者：
Bugge, TH;Lund, LR;Degen, JL
为了研究纤溶酶（原）在乳腺肿瘤发生和进展中的作用，将纤溶酶原缺陷型小鼠与在小鼠乳腺肿瘤病毒长末端重复序列控制下表达Polyoma中T抗原的转基因小鼠杂交。无论是否存在循环纤溶酶原，携带多瘤中T抗原的处女女性都会一致地产生多个双侧乳腺肿瘤。缺乏纤溶酶原的小鼠和表达纤溶酶原的同窝小鼠之间，这些肿瘤变得明显的年龄和随后的肿瘤生长都无法区分。然而，发现纤溶酶原极大地改变了该模型系统的转移潜力。与同窝对照小鼠相比，纤溶酶原缺陷小鼠的肺转移在发生频率、转移总数和总转移肿瘤负荷方面显着减少。纤溶酶原激活剂以及控制纤溶酶原转化为纤溶酶的其他关键因子在乳腺肿瘤内表达，表明纤溶酶原/纤溶酶系统可能通过促进肿瘤相关的细胞外蛋白水解来促进转移。这些数据提供了直接证据，表明纤溶酶（原）是 PymT 诱导的乳腺癌中的肿瘤进展因子，并支持止血因子在肿瘤生物学中发挥重要作用的假设。
To investigate the role of plasmin(ogen) in mammary tumor development and progression, plasminogen-deficient mice were crossed with transgenic mice expressing Polyoma middle T antigen under the control of the mouse mammary tumor virus long terminal repeat. Virgin females carrying the Polyoma middle T antigen uniformly developed multiple, bilateral mammary tumors, regardless of the presence or absence of circulating plasminogen. Both the age at which these tumors became palpable and subsequent tumor growth were indistinguishable between plasminogen-deficient mice and plasminogen-expressing littermates. Hoowever, plasminogen was found to greatly modify the metastatic potential in this model system; lung metastasis in plasminogen-deficient mice was significantly reduced as compared to littermate controls with respect to frequency of occurrence, total number of metastases, and total metastatic tumor burden. Plasminogen activators, as well as other key factors that govern the conversion of plasminogen to plasmin, were expressed within the mammary tumors, suggesting that the plasminogen/plasmin system may promote metastasis by contributing to tumor-associated extracellular proteolysis. The data provide direct evidence that plasmin(ogen) is a tumor progression factor in PymT-induced mammary cancer, and support the hypothesis that hemostatic factors play an important role in tumor biology.