Bugge T H, Kombrinck K W, Xiao Q, Holmbäck K, Daugherty C C, Witte D P, Degen J L
Divisions of Developmental Biology and Pathology, Children's Hospital Research Foundation, Cincinnati, OH, USA.
Blood. 1997 Dec 1;90(11):4522-31.
Plasminogen activation has been proposed to play a critical role in cancer invasion and metastasis. The effects of complete ablation of plasminogen activation in cancer was studied by inoculation of a metastatic Lewis lung carcinoma expressing high levels of plasminogen activator into plasminogen-deficient (Plg-/-) mice and matched control mice. Primary tumors developed in all mice with no difference in the rate of appearance between Plg-/- and control mice. However, the primary tumors in Plg-/- mice were smaller and less hemorrhagic and displayed reduced skin ulceration. In addition, dissemination of the tumor to regional lymph nodes was delayed in Plg-/- mice. Surprisingly, no quantitative differences were observed in lung metastasis between Plg-/- and control mice. In addition, Plg deficiency was compatible with metastasis of the primary tumor to a variety of other organs. Nevertheless, Plg-/- mice displayed a moderately increased survival after primary tumor resection. These findings suggest that plasmin-mediated proteolysis contributes to the morbidity and mortality of Lewis lung carcinoma in mice, but sufficient proteolytic activity is generated in Plg-/- mice for efficient tumor development and metastasis.
纤溶酶原激活被认为在癌症侵袭和转移中起关键作用。通过将表达高水平纤溶酶原激活剂的转移性刘易斯肺癌接种到纤溶酶原缺陷（Plg-/-）小鼠和匹配的对照小鼠中，研究了癌症中纤溶酶原激活完全缺失的影响。所有小鼠都出现了原发性肿瘤，Plg-/-小鼠和对照小鼠之间出现的速率没有差异。然而，Plg-/-小鼠中的原发性肿瘤较小，出血较少，皮肤溃疡也较少。此外，Plg-/-小鼠中肿瘤向区域淋巴结的扩散延迟。令人惊讶的是，Plg-/-小鼠和对照小鼠在肺转移方面没有观察到定量差异。此外，Plg缺陷与原发性肿瘤转移到多种其他器官是相容的。尽管如此，Plg-/-小鼠在原发性肿瘤切除后存活时间适度延长。这些发现表明，纤溶酶介导的蛋白水解作用导致小鼠刘易斯肺癌的发病和死亡，但在Plg-/-小鼠中产生了足够的蛋白水解活性以实现有效的肿瘤发展和转移。
