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首页> 美国卫生研究院文献>Cell Stress Chaperones >Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin MUC18/MCAM and plasminogen activator (PA) system
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Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin MUC18/MCAM and plasminogen activator (PA) system

机译：Hsp27在人黑素瘤细胞系中的过表达：E-钙粘蛋白MUC18 / MCAM和纤溶酶原激活物（PA）系统的调节

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Hsp27 is considered a potential marker for cell differentiation in diverse tissues. Several aspects linked to the differentiation process and to the transition from high to low metastatic potential were analyzed in melanoma cells transfected with Hsp27. E-cadherin plays a central role in cell differentiation, migration, and normal development. Loss of expression or function of E-cadherin has been documented in a variety of human malignancies. We observed by fluorescence-activated cell sorter (FACS) as well as immunofluorescence (IF) analysis a pronounced expression of E-cadherin in Hsp27-transfected A375 melanoma cells compared with control melanoma cells. The expression of the adhesion molecule MUC18/MCAM correlates directly with the metastatic potential of melanoma cells. In contrast to wild-type and neotransfected melanoma cells, in Hsp27-transfected cells the expression of MUC18/MCAM could not be detected by FACS and IF analysis. The plasminogen activator (PA) system plays a central role in mediating extracellular proteolysis and also in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. Hsp27 transfectants revealed elevated messenger ribonucleic acid expression of the urokinase-type PA (uPA) and its inhibitor, PA inhibitor type 1, which might indicate a neutralization effect of the proteolytic activity of uPA. Control cells failed to express both these molecules. The influence of Hsp27 expression on uPA activity and the involvement of E-cadherin could be demonstrated by use of anti–E-cadherin–blocking antibody. Our data provide evidence for an inhibitory-regulatory role of Hsp27 in tumor progression as found in our system.
机译：Hsp27被认为是多种组织中细胞分化的潜在标志。在用Hsp27转染的黑素瘤细胞中分析了与分化过程以及从高转移电位到低转移电位的转变有关的几个方面。 E-钙粘蛋白在细胞分化，迁移和正常发育中起着核心作用。 E-钙粘着蛋白的表达或功能丧失已在多种人类恶性肿瘤中记录。我们通过荧光激活细胞分选仪（FACS）以及免疫荧光（IF）分析观察到，与对照黑素瘤细胞相比，Hsp27转染的A375黑素瘤细胞中E-cadherin的表达明显。粘附分子MUC18 / MCAM的表达与黑色素瘤细胞的转移潜能直接相关。与野生型和新转染的黑色素瘤细胞相反，在Hsp27转染的细胞中，无法通过FACS和IF分析检测到MUC18 / MCAM的表达。纤溶酶原激活剂（PA）系统在介导细胞外蛋白水解以及非蛋白水解事件（例如细胞粘附，迁移和跨膜信号传导）中起着核心作用。 Hsp27转染子显示尿激酶型PA（uPA）及其抑制剂PA抑制剂1型的信使核糖核酸表达升高，这可能表明uPA的蛋白水解活性具有中和作用。对照细胞不能表达这两种分子。 Hsp27表达对uPA活性和E-cadherin参与的影响可以通过使用抗E-cadherin阻断抗体来证明。我们的数据提供了在我们系统中发现的Hsp27在肿瘤进展中的抑制调节作用的证据。

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