Mohan P M, Chintala S K, Mohanam S, Gladson C L, Kim E S, Gokaslan Z L, Lakka S S, Roth J A, Fang B, Sawaya R, Kyritsis A P, Rao J S
Department of Neurosurgery, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1999 Jul 15;59(14):3369-73.
The urokinase-type plasminogen activator (uPA) and uPA receptor (UPAR) play important roles in the proteolytic cascade involved in the invasiveness of gliomas and other invasive tumors. High-level expression of uPAR has been correlated with high-grade glioma cell lines and tumors We report here that down-regulating uPAR levels by antisense strategy using an adenovirus construct (Ad-uPAR) inhibited glioma invasion in Matrigel and spheroid in vitro models. sc. (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice. However, injection of the Ad-uPAR construct into previously established so U87-MG tumors in nude mice caused regression of those tumors. Our results support the therapeutic potential of targeting the uPA-uPAR system for the treatment of gliomas and other cancers.
尿激酶型纤溶酶原激活剂（uPA）和uPA受体（UPAR）在涉及胶质瘤和其他侵袭性肿瘤侵袭性的蛋白水解级联反应中发挥重要作用。UPAR的高表达与高级别胶质瘤细胞系和肿瘤相关。我们在此报告，使用腺病毒构建体（Ad-uPAR）通过反义策略下调uPAR水平可在体外基质胶和球体模型中抑制胶质瘤侵袭。皮下（U87-MG）和颅内（SNB19）注射Ad-uPAR感染的胶质瘤细胞在裸鼠中未产生肿瘤。然而，将Ad-uPAR构建体注射到裸鼠中先前建立的U87-MG肿瘤中会导致这些肿瘤消退。我们的结果支持靶向uPA-uPAR系统治疗胶质瘤和其他癌症的治疗潜力。
