Mohanam S, Chintala S K, Mohan P M, Sawaya R, Lagos G K, Gokaslan Z L, Kouraklis G P, Rao J S
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Oncol. 1998 Dec;13(6):1285-90. doi: 10.3892/ijo.13.6.1285.
The cell-surface urokinase plasminogen activator receptor (uPAR) plays a key role in regulating plasminogen cleavage during extracellular proteolysis. Our recent results demonstrated that uPAR expression is critical for the invasiveness of human gliomas and down regulation of uPAR caused by antisense cDNA transfection inhibits the invasion of these stable antisense uPAR-transfectant clones. To study the role of uPARs in glioma cell invasion, a human neuroglioma cell line (H4) that normally produces low numbers of uPARs was transfected with the expression vector containing full-length human uPAR cDNA. Stable transfectants were analyzed for uPAR mRNA expression, receptor number, in vitro invasion and secretion of uPA and MMP-2. The uPAR-overproducing clones showed a 4-fold increase in uPAR mRNA transcription and approximately 40% increase in receptor numbers. uPAR-overproducing clones also invaded through matrigel to a significantly greater extent than did parent cell line and vector clones. However, the uPAR-overexpressing clones and parent cell lines showed similar uPA and MMP-2 activities. These results suggest that the over-production of uPAR on the surface of neuroglioma cells enhances the invasiveness.
细胞表面尿激酶型纤溶酶原激活物受体（uPAR）在细胞外蛋白水解过程中调节纤溶酶原裂解起关键作用。我们最近的结果表明，uPAR表达对人类胶质瘤的侵袭性至关重要，反义cDNA转染引起的uPAR下调抑制了这些稳定的反义uPAR转染克隆的侵袭。为了研究uPAR在胶质瘤细胞侵袭中的作用，用含全长人uPAR cDNA的表达载体转染正常产生少量uPAR的人神经胶质瘤细胞系（H4）。分析稳定转染子的uPAR mRNA表达、受体数量、体外侵袭以及uPA和MMP-2的分泌。uPAR过度产生的克隆显示uPAR mRNA转录增加4倍，受体数量增加约40%。uPAR过度产生的克隆通过基质胶侵袭的程度也明显大于亲本细胞系和载体克隆。然而，uPAR过表达克隆和亲本细胞系显示出相似的uPA和MMP-2活性。这些结果表明神经胶质瘤细胞表面uPAR的过度产生增强了侵袭性。
