Mignatti P, Robbins E, Rifkin D B
Cell. 1986 Nov 21;47(4):487-98. doi: 10.1016/0092-8674(86)90613-6.
To understand the role of proteinases in tumor invasion, the effects of inhibitors of metallo-, serine-, and cysteine-proteinases on this process were studied using 125I-iododeoxyuridine-labeled B16/BL6 cells grown on human amnion basement membrane. Cellular invasion was quantitated by measuring the radioactivity associated with the amniotic membrane after the B16/BL6 cells on the basement membrane were removed by lysis followed by scraping. The results obtained with proteinase inhibitors showed that inhibitors of collagenase and plasmin prevented invasion of the amnion. Tissue invasion was also blocked by antiurokinase antibodies. On the contrary, cysteine-proteinase inhibitors and anti-tissue plasminogen activator antiserum were ineffective. Mersalyl, a compound known to activate collagenase, stimulated invasion under conditions where plasmin formation or activity were inhibited. Evidence for the role of a plasminogen activator-plasmin-collagenase activation cascade in B16 invasion is provided.
为了解蛋白酶在肿瘤侵袭中的作用，使用在人羊膜基底膜上生长的125I - 碘脱氧尿苷标记的B16/BL6细胞，研究了金属蛋白酶、丝氨酸蛋白酶和半胱氨酸蛋白酶抑制剂对这一过程的影响。通过在裂解后刮除基底膜上的B16/BL6细胞，测量与羊膜相关的放射性来定量细胞侵袭。蛋白酶抑制剂的实验结果表明，胶原酶和纤溶酶抑制剂可阻止羊膜侵袭。抗尿激酶抗体也能阻断组织侵袭。相反，半胱氨酸蛋白酶抑制剂和抗组织纤溶酶原激活物抗血清无效。已知能激活胶原酶的化合物汞撒利，在纤溶酶形成或活性受到抑制的条件下刺激侵袭。这为纤溶酶原激活物 - 纤溶酶 - 胶原酶激活级联在B16侵袭中的作用提供了证据。
