Mazar A P, Henkin J, Goldfarb R H
Angstrom Pharmaceuticals, Department of Tumor Biology, 11585 Sorrento Valley Rd, Suite 105, San Diego, CA 92121, USA.
Angiogenesis. 1999;3(1):15-32. doi: 10.1023/a:1009095825561.
Substantial evidence exists which implicates the urokinase plasminogen activator system [urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1)] in the neo-vascularization, invasion and metastasis of many solid tumors. Clinical studies have demonstrated an association between high levels of expression of the components of this system in tumors and poor patient prognosis and outcome. Components of the uPA/uPAR system are differentially expressed or activated on motile cells including invading tumor cells and leukocytes, and migrating endothelial cells. In contrast, there is little or no expression on most normal, quiescent cells. Studies performed in vitro have demonstrated the regulation of the expression of uPA and uPAR by growth and differentiation factors as well as by oncogenes. In this review, we summarize recent findings on the role of the components of the uPA/uPAR system in angiogenesis, invasiveness and tumor metastasis. The activities of this system in endothelial and leukocyte cell biology and the relevance of these activities to angiogenesis and tumor metastasis will be considered. Recent experimental evidence obtained using inhibitors of uPA and uPAR has validated this system as a therapeutic target for the development of anti-angiogenic and anti-metastatic therapeutic agents. These studies, as well as additional therapeutic and diagnostic implications for uPAR targeting, will be discussed.
有大量证据表明，尿激酶纤溶酶原激活系统[尿激酶纤溶酶原激活剂（uPA）、尿激酶纤溶酶原激活剂受体（uPAR）和纤溶酶原激活剂抑制剂-1（PAI-1）]与许多实体瘤的新血管形成、侵袭和转移有关。临床研究表明，该系统各组分在肿瘤中的高表达水平与患者预后不良相关。uPA/uPAR系统的组分在包括侵袭性肿瘤细胞和白细胞以及迁移的内皮细胞在内的运动细胞上有差异表达或被激活。相比之下，大多数正常静止细胞几乎不表达或不表达。体外研究表明，生长和分化因子以及癌基因可调节uPA和uPAR的表达。在这篇综述中，我们总结了uPA/uPAR系统各组分在血管生成、侵袭和肿瘤转移中作用的最新研究结果。将考虑该系统在内皮细胞和白细胞生物学中的活性以及这些活性与血管生成和肿瘤转移的相关性。使用uPA和uPAR抑制剂获得的最新实验证据已证实该系统是开发抗血管生成和抗转移治疗药物的治疗靶点。将讨论这些研究以及针对uPAR的其他治疗和诊断意义。
