Bhuvarahamurthy Venugopal, Schroeder Joerg, Kristiansen Glen, Roigas Jan, Denkert Carsten, Johannsen Manfred, Lein Michael, Loening Stefan A, Schnorr Dietmar, Jung Klaus, Staack Andrea
Department of Urology, University Hospital Charité, Humboldt University Berlin, D-10098 Berlin, Germany.
Oncol Rep. 2005 Sep;14(3):777-82.
The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.
尿激酶型纤溶酶原激活剂（uPA）系统在细胞外基质降解、细胞迁移和侵袭过程中起着核心作用。uPA属于丝氨酸蛋白酶家族。研究表明，其蛋白水解活性通过激活并与其受体（uPAR）结合而参与转移过程。先前在多个器官系统中的研究表明，与正常组织相比，恶性组织中uPA表达更高。在本研究中，对18例人类肾细胞癌（RCC）标本及其相邻的非恶性肾组织进行了uPA和uPAR基因表达的研究。进行了mRNA原位杂交和免疫组织化学染色。与相邻的非恶性肾组织相比，uPA和uPAR的mRNA在56%（10/18）和72%（13/18）的RCC标本中表达显著更高（p<0.0001）。uPA-mRNA和uPAR-mRNA主要在恶性肾细胞中表达，在极少的周围基质细胞中也有表达。与相邻正常组织相比，RCC中uPAR蛋白的表达升高具有统计学意义（p=0.007）。与单独的uPA相比，uPAR基因表达更高。有统计学趋势表明，uPA和uPAR的高表达与RCC的TNM肿瘤分期和分级相关。需要用更大的样本量进行进一步研究，以证明uPA和uPAR的表达与更具侵袭性的表型之间的相关性。我们得出结论，uPA和uPAR在RCC中过度表达，可作为肿瘤标志物。
