Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system
Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system
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DOI：
10.1002/ijc.20192
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发表时间：
2004-07-20
影响因子：
6.4
通讯作者：
Gires, O
中科院分区：
文献类型：
--
作者：
Ertongur, S;Lang, S;Gires, O
癌症患者的总体存活率一直很低，在过去几十年里几乎没有变化。这主要是由于所谓的微小残留病，即残留的肿瘤细胞克服了手术和/或放射治疗，是局部和远处转移的原因。为了转移，肿瘤细胞利用蛋白水解酶侵袭并重塑周围组织。在这里，我们分析了WX-UK1，一种新型的基于3-氨基苯丙氨酸的uPA系统抑制剂，在抑制癌细胞侵袭能力方面的效率。首先，uPAR在不同的癌细胞系中的表达特征，包括SCCHN、乳腺癌和宫颈癌。然后，利用Matrigel侵袭小室和人成纤维细胞的球状共培养模型来确定这些细胞系的侵袭潜能。UPAR表达水平与侵袭能力呈正相关，WX-UK1可显著抑制uPAR的表达。经WX-UK1处理后，SCCHN细胞株FaDu和宫颈癌细胞系HeLa的肿瘤细胞侵袭力均降低了50%。因此，我们的结果证明了WX-UK1在体外作为一种有前途的肿瘤辅助抗转移治疗的潜力。(C)2004年Wiley-Liss公司
The overall survival rate of patients suffering from carcinomas has remained poor and nearly unchanged over the last decades. This is mainly due to the so-called minimal residual disease, i.e., remaining tumor cells that overcome surgery and/or radiotherapy and are the cause of locoregional and distant metastases. To metastasize, tumor cells take advantage of proteases to invade and remodel surrounding tissues. Here, we analyzed the efficiency of WX-UK1, a novel 3-amidinophenylalanine-based inhibitor of the uPA system, at inhibiting the invasive capacity of carcinoma cells. First, uPAR expression was characterized in different carcinoma cell lines, including SCCHN, breast and cervical carcinoma. Thereafter, the invasive potential of these cell lines was determined using Matrigel invasion chambers and a spheroid cocultivation model with human fibroblasts. uPAR expression levels correlated positively with invasion capacity, which could be significantly inhibited by WX-UK1. A decrease of tumor cell invasion by up to 50% was achieved in both models with the SCCHN line FaDu and the cervical carcinoma line HeLa after treatment with WX-UK1. Thus, our results demonstrate the potential of WX-UK1 in vitro as a promising adjuvant antimetastatic therapy of carcinomas. (C) 2004 Wiley-Liss, Inc.