Wilhelm O, Schmitt M, Höhl S, Senekowitsch R, Graeff H
Frauenklinik der Technischen Universität München, Germany.
Clin Exp Metastasis. 1995 Jul;13(4):296-302. doi: 10.1007/BF00133485.
Urokinase-type plasminogen activator (uPA) is a protease involved in the process of tissue remodelling and cell migration in vitro. To explore whether uPA is a prerequisite for human ovarian cancer spread in vivo the expression of uPA was suppressed in human ovarian cancer cells by antisense phosphorothioate oligonucleotides (PS-ODN). The suppression of uPA expression was dependent on PS-ODN concentration and only observed in the presence of liposomes. This phenomenon seemed to be due to the fact that PS-ODNs were taken up by the cancer cells only in concert with liposomes as studied by fluorescently-labeled PS-ODNs using flow cytofluorometry and laser scanning microscopy. uPA-deprived cancer cells exhibited a significantly reduced invasive capacity in vitro compared with untreated cancer cells or cells treated with control PS-ODNs (P = 0.003). The intraperitoneal spread of the cancer cells in vivo was significantly diminished when nude mice were treated with uPA antisense PS-ODNs in comparison with control mice (P = 0.009). These results suggest that uPA expression may be required for spread of human ovarian cancer and that its inhibition could provide a therapeutic approach.
尿激酶型纤溶酶原激活剂（uPA）是一种参与体外组织重塑和细胞迁移过程的蛋白酶。为了探究uPA是否是人类卵巢癌在体内扩散的必要条件，采用反义硫代磷酸酯寡核苷酸（PS-ODN）抑制人卵巢癌细胞中uPA的表达。uPA表达的抑制取决于PS-ODN的浓度，且仅在脂质体存在时才会观察到。通过流式细胞荧光术和激光扫描显微镜对荧光标记的PS-ODN进行研究，发现这种现象似乎是由于PS-ODN仅与脂质体协同作用时才会被癌细胞摄取。与未处理的癌细胞或用对照PS-ODN处理的细胞相比，缺乏uPA的癌细胞在体外的侵袭能力显著降低（P = 0.003）。与对照小鼠相比，用uPA反义PS-ODN处理裸鼠时，癌细胞在体内的腹膜扩散明显减少（P = 0.009）。这些结果表明，uPA的表达可能是人类卵巢癌扩散所必需的，抑制其表达可能提供一种治疗方法。
