Transformational Alteration of Human pancreatic Gamma-Glutamyl-transpeptidase (gamma-GTP)

为阐明胰腺γ-谷氨酰转肽酶（gamma-glutamltranspeptidase，γ-GTP）在恶性转化过程中的特异性变化，将胰腺癌组织中纯化的γ-GTP与正常胰腺及其它组织中的γ-GTP进行了比较。五分之四的胰腺癌γ-GTP表现出明显慢于正常酶的电泳迁移率。胰腺癌γ-GTP的等电点在每种情况下都不同，但它们都高于正常酶。通过神经氨酸酶处理，癌组织和正常组织之间的γ-GTP的等电点的这种差异减小。凝集素亲和层析显示，五个胰腺癌γ-GTP与刀豆球蛋白A（Con A）的亲和力比正常胰腺γ-GTP更大。五个胰腺癌γ-GTP中的四个与透镜culinaris凝集素（LCA）的亲和力大于正常胰腺γ-GTP。正常胰腺对菜豆的亲和性很低 ...更多信息 Garis红细胞凝集素（E-PHA），而胰腺癌γ-GTP中有2个对E-PHA有明显的亲和力，1个对E-PHA有微弱的亲和力。这些结果表明，胰腺癌γ-GTP的转化变化主要是在酶分子的糖链上引起的，与正常胰腺酶相比，其唾液酸含量较低，岩藻糖含量较高，GlcNAc残基一分为二。我们利用杂交瘤技术制备了抗胰腺癌γ-GTP的单克隆抗体。所有单抗均能与胰腺癌及其他组织中的γ-GTP反应，但不能识别γ-GTP的糖链，只能识别γ-GTP的肽段。这被认为是由于糖链的免疫原性与肽部分的免疫原性相比可能更弱的事实。我们现在正在准备特定的单克隆抗体，考虑一种新的设备。少

To elucidate the specific changes of pancreatic gamma-glutamltranspeptidase (gamma-GTP) associated with malignant transformation, some properties of gama-GTP purified from pancreatic cancer were compared with those of gamma-GTPs from normal pancreas and other tissues. Four of five pancreatic cancer gamma-GTPs showed distinctly slower electrophoretic mobility than the normal enzymes. Isoelectric points of pancreatic cancer gamma-GTPs varied in each case, but all of them were higher than those of normal enzymes. This difference in isoelectric points of gamma-GTPs between cancerous tissue and normal tissue was reduced by neuraminidase treatment. Lectin affinity chromatography revealed two of five pancreatic cancer gamma-GTPs with a greater affinity to concanavalin A (Con A) than normal pancreas gamma-GTPs. Four of five pancreatic cancer gamma-GTPs had a greater affinity to Lens culinaris agglutinin (LCA) than normal pancreas gamma-GTPs. Normal pancreas had little affinity to phaseolus vul … More garis erythroagglutinating (E-PHA), but two of five pancreatic cancer gamma-GTPs had an apparent affinity to E-PHA and one of them had a slight affinity to E-PHA. These results indicate that the transformational changes of pancreatic cancer gamma-GTP are mainly induced in the sugar chains of the enzyme molecules resulting in a lower content of sialic acid and higher content of fucose and bisecting GlcNAc residue as compared with the normal pancreatic enzymes.Furthermore, to develop the monoclonal antibody (MAb) that recognize the specific alteration of sugar chain of pancreatic cancer gamma-GTP, we prepared the MAb against gamma-GTP from pancreatia cancer using the hybridoma technique. All of the MAbs were reactive with gamma-GTPs from not only pancreatic cancers but also other tissues, and could not recognize sugar chain but peptide portion of gamma-GTP. This is considered to be due to the fact that the immunogenicity of sugar chain can be weaker in comparison with that of peptide portion. We are now preparing the specific MAb, considering a new device. Less