de Bock Charles Edo, Wang Yao
Orthopaedic Research Institute, St. George Hospital, University of New South Wales, Kogarah, Sydney, NSW 2217, Australia.
Med Res Rev. 2004 Jan;24(1):13-39. doi: 10.1002/med.10054.
The involvement of the urokinase-type plasminogen activator (uPA) system in particular has been extensively studied in the pathogenesis of cancer. The molecular role of the uPA receptor (uPAR) is well characterized with its participation in cell migration and extracellular matrix (ECM) degradation. Over-expression of uPAR in cancer has been demonstrated in many studies and is considered an attractive target for anticancer agents. We and others have down-regulated uPAR expression in an attempt to inhibit cancer metastasis based on its molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored protein is not only bound to the cell surface but also has a soluble form, suPAR. There is now accumulated clinical and experimental evidence supporting the significant role of uPAR and its soluble counterpart in a number of solid cancers. The expression of uPAR can be associated with tumor cells or stromal cells or both. Differences observed in the expression of uPAR using immunohistochemistry (IHC) are likely explained by the use of different antibodies and techniques rather than true cellular differences and are reviewed here. This review summarizes the clinical relevance of uPAR and its soluble form in the prognosis and diagnosis of different cancers.
尤其是尿激酶型纤溶酶原激活物（uPA）系统在癌症发病机制中的作用已得到广泛研究。uPA受体（uPAR）的分子作用已得到充分表征，它参与细胞迁移和细胞外基质（ECM）降解。许多研究已证实癌症中uPAR的过度表达，并且它被认为是抗癌药物的一个有吸引力的靶点。基于其分子作用，我们和其他人已下调uPAR表达以试图抑制癌症转移。独特的是，uPAR作为一种糖基磷脂酰肌醇锚定蛋白，不仅与细胞表面结合，而且还有一种可溶性形式，即suPAR。现在有越来越多的临床和实验证据支持uPAR及其可溶性对应物在多种实体癌中的重要作用。uPAR的表达可能与肿瘤细胞或基质细胞或两者都有关。使用免疫组织化学（IHC）观察到的uPAR表达差异可能是由于使用了不同的抗体和技术，而非真正的细胞差异，本文对此进行综述。本综述总结了uPAR及其可溶性形式在不同癌症预后和诊断中的临床相关性。
