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

人胰腺γ-谷氨酰转肽酶（γ-GTP）的转化改变

• 批准号: 63570318
• 负责人: SAWABU Norio
• 金额: $ 1.34万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570318/
• 关键词: gamma-GTP; Pancreatic Cancer; Sugar chain; Hepatocellular Carcinoma; Monoclonal antibody; Transformational alteration; 糖鎖構造; γ-glutamyl transpeptidase(γ-GTP)

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

为阐明胰腺癌组织中γ-谷氨酰转肽酶(GAMA-GTP)在癌变过程中的特异性变化，我们比较了从胰腺癌组织中提纯的GAMA-GTP与从正常胰腺和其他组织中提取的GAMA-GTP的某些性质。五分之四的胰腺癌γ-GTP表现出明显慢于正常酶的电泳率。胰腺癌γ-GTP等电点各不相同，但均高于正常酶等电点。神经氨酸酶处理缩小了癌组织和正常组织之间的伽马-GTP等电点的差异。凝集素亲和层析显示五种胰腺癌γ-GTP中有两种对刀豆蛋白A(ConA)的亲和力高于正常胰腺。与正常胰腺组织相比，5个胰腺癌γ-GTP中有4个对晶状体凝集素(LCA)有更强的亲和力。正常胰腺对菜豆VUL…几乎没有亲和力5个胰腺癌γ-GTP中有2个与E-PHA有明显亲和力，其中1个与E-PHA有轻微亲和力。这些结果表明，与正常胰腺酶相比，胰腺癌γ-GTP的转化主要是在酶分子的糖链中诱导的，导致唾液酸含量较低，岩藻糖含量较高，GlcNAc残基一分为二。此外，为了研制识别胰腺癌γ-GTP糖链特异性变化的单抗，我们利用杂交瘤技术制备了抗胰腺癌γ-GTP的单抗。所有单抗均能与胰腺癌及其他组织中的γ-GTP反应，且不能识别γ-GTP的糖链和多肽部分。这被认为是由于糖链的免疫原性可能比多肽部分弱。我们现在正在准备特定的单抗，考虑一种新的设备。较少

项目成果

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Y. Satomura 等人：“恶性和非恶性胰腺组织中各种唾液酸化碳水化合物抗原的表达”胰腺。

澤武紀雄ほか: "消化器癌における癌性糖鎖抗原" 臨床病理. 37. 509-516 (1989)

Takeo Sawa 等：“胃肠癌中的癌症糖链抗原”临床病理学 37. 509-516 (1989)。

太田英樹 他: 第7回腫瘍マーカー研究会プロシーデングス. 3. 220-222 (1988)

Hideki Ota 等人：第七届肿瘤标志物研究组论文集。3. 220-222 (1988)。

澤武紀雄ほか: "膵腫瘍マ-カ-の現状" 消化器科. 10. 640-649 (1989)

Takeo Sawa 等人：“胰腺肿瘤标志物的现状”胃肠病学 10. 640-649 (1989)。

Hideki Ohta,et al.: "Characterization of γ-GTP from hepatocellular carcinoma、and comparison with enzymes from normal liver、cintrotic liver and other tissues" Hepatology.

Hideki Ohta 等人：“肝细胞癌中 γ-GTP 的表征，以及与正常肝脏、中心性肝脏和其他组织中的酶的比较”肝病学。