Alterations in cathepsin L expression and trafficking have been associated with the progression and metastasis of several tumor entities. In the present study, we examined the effects of various cathepsin L antisense (as) phosphorothioate oligonucleotides on both the expression of cathepsin L and the invasive potential of the human osteosarcoma cell line MNNG/HOS. Seven oligonucleotides of 20-bp length each and one random control oligonucleotide were chosen to block cathepsin L expression. Northern blot analysis demonstrated a significant reduction in cathepsin L mRNA expression by the six antisense oligonucleotides at a concentration of 10 microM. Cathepsin L protein expression was reduced significantly (50-85%) by the antisense oligonucleotides, as compared with the controls. Adhesion to matrices of collagen I and matrigel was not affected. In in vitro motility and invasion assays performed in uncoated and precoated transwell chambers, the ability of cells to migrate through the filters was inhibited by 35-75% using antisense oligonucleotides. The random control did not show any inhibitory effect. These data demonstrate that in MNNG/HOS cells cathepsin L influences cellular malignancy by promoting migration and basement membrane degradation.

中文翻译：

---

人骨肉瘤细胞系中的组织蛋白酶L反义寡核苷酸：对侵袭性表型的影响。

组织蛋白酶L表达和运输的改变与几种肿瘤实体的进展和转移有关。在本研究中，我们检查了各种组织蛋白酶L反义（as）硫代磷酸酯寡核苷酸对组织蛋白酶L的表达和人骨肉瘤细胞系MNNG / HOS的侵袭潜力的影响。选择七个各自长度为20 bp的寡核苷酸和一个随机对照寡核苷酸来阻断组织蛋白酶L的表达。Northern印迹分析表明，在浓度为10 microM时，六个反义寡核苷酸可显着降低组织蛋白酶L mRNA的表达。与对照相比，反义寡核苷酸使组织蛋白酶L蛋白表达显着降低（50-85％）。胶原蛋白I和基质胶对基质的附着力不受影响。在未涂覆和预涂覆的transwell腔室中进行的体外运动和侵袭试验中，使用反义寡核苷酸可将细胞迁移通过滤膜的能力抑制35-75％。随机对照未显示任何抑制作用。这些数据表明，在MNNG / HOS细胞中，组织蛋白酶L通过促进迁移和基底膜降解来影响细胞恶性肿瘤。