Reiter L S, Spertini O, Kruithof E K
Department of Medicine, University Hospital Lausanne, Switzerland.
Int J Cancer. 1997 Feb 7;70(4):461-6. doi: 10.1002/(sici)1097-0215(19970207)70:4<461::aid-ijc14>3.0.co;2-i.
Involvement of extravascular sites, in particular infiltration of the central nervous system, is a frequent complication of T-lymphoblastic leukemia and contributes to leukemia-associated morbidity. In this report, we studied the contribution of plasminogen activators to the invasive properties of 7 human T-cell lines in a model of transmigration through an extracellular matrix. The T-cell lines were found to express either urokinase (u-PA) and high levels of u-PA receptor or tissue-type plasminogen activator (t-PA) and low levels of u-PA receptor. The rate of transmigration was consistently higher for u-PA-expressing cells than for t-PA-expressing cells. PA-inhibitor type 1 (PAI-1) was detected in the conditioned medium of one cell line and PAI-2 was detected in cell extracts from 6 lines. The transmigration of 6 out of 7 cell lines was inhibited by trasylol, an inhibitor of plasmin, by an excess of exogenous PAI-1 or PAI-2, and by antibodies to the particular PA type expressed by the cells. Partial inhibition of transmigration by the amino-terminal fragment of u-PA implies that the u-PA receptor contributes to transmigration. Thus, the transmigration of T-leukemia cells through a barrier of extracellular matrix requires PA-dependent proteolysis, which can be provided either by u-PA or t-PA. Specific inhibition of the PA system could provide a means to inhibit tissue invasion by T lymphoblastic cells.
血管外部位受累，尤其是中枢神经系统浸润，是T淋巴细胞白血病的常见并发症，并导致白血病相关的发病率。在本报告中，我们在一个通过细胞外基质迁移的模型中研究了纤溶酶原激活剂对7种人T细胞系侵袭特性的作用。发现这些T细胞系要么表达尿激酶（u-PA）和高水平的u-PA受体，要么表达组织型纤溶酶原激活剂（t-PA）和低水平的u-PA受体。表达u-PA的细胞的迁移率始终高于表达t-PA的细胞。在一种细胞系的条件培养基中检测到1型PA抑制剂（PAI-1），在6种细胞系的细胞提取物中检测到PAI-2。7种细胞系中的6种细胞系的迁移受到抑肽酶（一种纤溶酶抑制剂）、过量的外源性PAI-1或PAI-2以及针对细胞表达的特定PA类型的抗体的抑制。u-PA氨基末端片段对迁移的部分抑制表明u-PA受体有助于迁移。因此，T白血病细胞通过细胞外基质屏障的迁移需要PA依赖性蛋白水解，这可以由u-PA或t-PA提供。对PA系统的特异性抑制可以提供一种抑制T淋巴细胞母细胞组织侵袭的方法。
