Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-α or basic fibroblast growth factor
Up-regulation of urokinase-type plasminogen activator and its receptor correlates with enhanced invasion activity of human glioma cells mediated by transforming growth factor-α or basic fibroblast growth factor
复制标题
DOI：
10.1023/a:1006339717748
复制
发表时间：
2000-01-01
影响因子：
3.9
通讯作者：
Hori, S
中科院分区：
文献类型：
--
作者：
Mori, T;Abe, T;Hori, S
多形性胶质母细胞瘤是一种高度恶性的肿瘤，极难治疗。其中一个原因是它对脑组织具有高度侵入性。金属蛋白酶及其抑制物、纤溶酶原激活物(PA)及其抑制物和组织蛋白被认为与肿瘤细胞的侵袭有关。在这项研究中，我们确定了尿激酶型纤溶酶原激活物(UPA)和/或尿激酶型纤溶酶原激活物受体(UPAR)是否与人脑胶质瘤细胞系的侵袭活性有关。我们用体外侵袭实验系统测定了人脑胶质瘤U251细胞系的侵袭活性。在碱性成纤维细胞生长因子或转化生长因子-α的存在下，侵袭活性增加了2.4-5.8倍。Northern印迹分析表明，bFCF和转化生长因子-α处理与细胞内uPA和uPAR的mRNA水平升高有关。酶谱活性与uPA和uPAR基因表达水平相关。加入抗uPAR单抗可显著抑制bFGF-α和转化生长因子-α诱导的侵袭活性。UPA合成的抑制剂伊索拉定也阻断了侵袭活性。这些观察结果表明，uPA及其受体在人脑胶质瘤的侵袭过程中发挥了作用。
Glioblastoma multiforme is a highly malignant tumor that is extremely refractory to therapy. One reason is its highly invasive nature into brain tissue. Metalloproteinases and their inhibitors, plasminogen activators (PA) and their inhibitors and cathepsins are thought to be involved in invasion by tumor cells. In this study, we determined if the urokinase-type plasminogen activator (uPA) and/or the urokinase-type plasminogen activator receptor (uPAR) were responsible for the invasion activity of a human glioma cell Line. We determined the invasion activity of a human glioma U251 cell line using an in vitro invasion assay system. A 2.4- to 5.8-fold increase in invasion activity was observed in the presence of basic fibroblast growth factor (bFGF) or transforming growth factor (TGF)-alpha. Northern blot analysis showed that bFCF and TGF-alpha treatment was associated with increases in cellular mRNA levels of uPA and uPAR. Zymographic activity correlated to mRNA levels of uPA and uPAR. Addition of an anti-uPAR monoclonal antibody significantly inhibited the invasion activity induced by bFGF- and TGF-alpha. Irsogladine, an inhibitor of uPA synthesis, also blocked the invasion activity. These observations suggest that uPA and its receptor have a role in the invasion process of human gliomas.