Analyzes of the role of urokinase receptor cell growth

(1)研究uPAR mPNA在培养的U-937细胞中的表达。佛波酯刺激后，uPAR基因的表达增强，从而导致uPAR抗原在培养液和细胞裂解液中的积聚增加。我们检测到两种不同形式的uPAR mRNA，一种是编码可溶性uPAR，另一种是编码可溶性uPAR。我们使用两种不同的DNA探针，每个探针只检测到这两种不同的mRNAs中的一种，我们发现这两种形式的uPAR在佛波酯刺激后都会增加。(2)我们检测了癌症患者血浆中可溶性uPAR的抗原水平。肺癌患者血浆可溶性uPAR水平显著高于正常对照组。无论是通过蛋白水解性切割成熟的uPAR，还是通过增加选择性剪接的可溶性uPAR的mRNA，血浆uPAR似乎都升高了。血浆可溶性uPAR水平可能是肺癌的一个有用的肿瘤标志物。(3)肺癌组织中uPA mRNA的表达明显高于正常肺组织。而癌组织和正常肺组织中uPAR基因的表达差异无统计学意义。肺癌组织中PAI-1和PAI-2的表达水平也高于正常肺组织，这与我们先前对其抗原水平的研究结果一致。(4)我们利用U937分析了uPA单独或联合uPA及其特异性抑制物对细胞生长的影响。UPA单独使用可轻微促进细胞生长。然而，同时使用其抑制剂并不影响细胞生长。由于未经佛波酯处理的U937细胞表面可能没有足够数量的uPAR，因此必须用其他细胞株进行进一步的实验，以阐明uPA及其抑制剂对细胞生长的影响。

(1) We studied the expression of uPAR mPNA in cultured cell line (U-937). The expression of uPAR mRNA was enhanced by phorbol-ester stimulation, which resulted in the higher accumulation of uPAR antigen both in the medium and in the cell lysate. We detected two different forms of uPAR mRNA,one of which coodes mature uPAR and another codes soluble uPAR.Employing two different DNA probes, each of which detects only one of these two different mRNAs, we demonstrated that both forms increased after phorbol ester stimulation.(2) We assayd antigen levels of soluble uPAR in cancer patients plasma. In lung cancer patients, plasma soluble uPAR levels were significantly higher than those in normal controls. Either by proteolytic cleavage of mature uPAR or by increasing alternatively spliced mRNA for soluble uPAR,plasma uPAR seems to be elevated. Plasma soluble uPAR level might be a useful tumor marker of lung cancer.(3) The expression of uPA mRNA in lung cancer tissue was significantly higher than that in normal lung tissue. The expression of uPAR mRNA,however, did not differ between cancer tissue and normal lung tissue. mRNA of both PAI-1 and PAI-2 were also higher in lung cancer tissue than those in normal counter parts, which are in accordance with our previous results of their antigen level.(4) We analyzed the effects of either uPA alone or of uPA together with its specific inhibitor on cell growth using U937. uPA alone slightly enhanced cell growth. Simultancous use of its inhibitor, however, did not influence cell growth. Since U937 without treatment by phorbol-ester may not have enough amounts of uPAR on cell surface, further experiment using other cell line must be needed to clarify the effect of uPA and its inhibitors on cell growth.