Boike G, Lah T, Sloane B F, Rozhin J, Honn K, Guirguis R, Stracke M L, Liotta L A, Schiffmann E
Department of Pharmacology, Wayne State University, Detroit, MI.
Melanoma Res. 1992 Jan-Feb;1(5-6):333-40. doi: 10.1097/00008390-199201000-00004.
The metastasis of malignant tumour cells depends on their rapid replication, and their ability to adhere to the matrix of a biological barrier such as basement membrane, to degrade the matrix, and to migrate through this more permeable barrier. Secreted enzymes, including the cysteine proteinases cathepsins B and L, are known to degrade basement membrane components. Using a barrier-free substratum we studied the possible role of cysteine proteinases in influencing the motility per se of metastatic cells. We found that stefins, the natural inhibitors of cysteine proteinases, markedly decreased the stimulated motility of both human melanoma cells and W256 carcinosarcoma cells at low concentrations (0.5 microM). A stefin also inhibited melanoma cell adherence, but to a lesser extent than motility. Additionally, synthetic inhibitors (E-64, diazomethyl ketones) of cysteine proteinases were found to depress stimulated motility of W256 cells. These results suggest that cysteine proteinases and their inhibitors may have a direct role in the development of a migratory response per se in tumour cells.
恶性肿瘤细胞的转移取决于其快速复制的能力，以及它们黏附于生物屏障（如基底膜）基质、降解该基质并穿过这一通透性更高的屏障进行迁移的能力。已知包括半胱氨酸蛋白酶组织蛋白酶B和L在内的分泌酶可降解基底膜成分。我们使用无屏障基质研究了半胱氨酸蛋白酶在影响转移细胞自身运动性方面可能发挥的作用。我们发现，半胱氨酸蛋白酶的天然抑制剂丝抑蛋白在低浓度（0.5微摩尔）时可显著降低人黑色素瘤细胞和W256癌肉瘤细胞的刺激运动性。一种丝抑蛋白还可抑制黑色素瘤细胞的黏附，但抑制程度低于对运动性的抑制。此外，还发现半胱氨酸蛋白酶的合成抑制剂（E-64、重氮甲基酮）可抑制W256细胞的刺激运动性。这些结果表明，半胱氨酸蛋白酶及其抑制剂可能在肿瘤细胞迁移反应的发生过程中直接发挥作用。
