Analysis of cancer metastasis to lymphnodes through lymphocyte adhesion molea

淋巴细胞粘附痣分析癌症淋巴结转移

• 批准号: 05670985
• 负责人: KATO Hirotaka
• 金额: $ 1.02万
• 依托单位: Tohoku 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670985/
• 关键词: metastasis; carcinoma; adhesion; モノクローナル抗体DG20; 細胞接着; Molt17; 細胞間相互作用; モノクロナール抗体

Recently, the development of tumor metastasis to lymphnodes has been considered to require direct adhesive interaction between tumor cells and lymphoid stromal cells. The study was performed by focusing on the involvement of adhesion molecules in metastatic process. In culture condition, Jurkat lymphoma cells bind to the surface of the stromal cells and Molt-4 cells crawl under the cytoplasm of stromal cells. We produced Mab DG-20 and DG-64 by immunizing rats with Jurkat and Molt-4 lymphoma cells, respectively. These lymphoma cells binding to the stroma was specifically inhibited with Mab DG-20 or DG-64. In this experiment, it is also necessary to establish human tumor cell lines which have a tendency to metastasize to lymphnodes or distant organs in the rodent model. To this end, we have established human thyroid carcinoma lines TA-K,TA-N,TA-M and TA-G,which were identified as anaplastic cancer cells by pathological criteria and the expression of keratin. Immunohistochemical analysis revealed high expression of sialyl Lex in all cell lines, no expression of E-cadherin or alpha-catenin in all lines. The expression of beta-catenin was positive in TA-K,TA-N and TA-M,and low positive in TA-G.Low expression of DG-20 or DG-64 was demonstrated by immunohistological examination. In vitro production of cytokiens were all examined. Various cytokines (IL-1, IL-2, IL-6, IL-7, IL-8, TNF alpha、G-CSF,GM-CSF) were produced in each cell line.

近年来，肿瘤转移到淋巴结的发展被认为需要肿瘤细胞和淋巴基质细胞之间的直接黏附作用。这项研究的重点是黏附分子在转移过程中的参与。在培养条件下，Jurkat淋巴瘤细胞与基质细胞表面结合，Molt-4细胞在基质细胞胞浆下爬行。我们分别用Jurkat和Molt-4淋巴瘤细胞免疫大鼠，制备了单抗DG-20和DG-。单抗DG-20或DG-对这些与间质结合的淋巴瘤细胞具有特异性抑制作用。在这项实验中，还有必要建立有转移趋势的人类肿瘤细胞系，在啮齿动物模型中转移到淋巴结或远处器官。为此，我们建立了人甲状腺癌细胞系TA-K、TA-N、TA-M和TA-G，经病理学和角蛋白表达鉴定为间变性癌细胞。免疫组织化学分析显示，所有细胞系唾液酸化Lex均高表达，E-钙粘附素和α-连环素均不表达。β-连环蛋白在TA-K、TA-N和TA-M中呈阳性表达，在TA-G中呈弱阳性表达，免疫组织学检查显示DG-20和DG-低表达。检测细胞因子的体外产生情况。每株细胞均产生多种细胞因子(IL-1、IL-2、IL-6、IL-7、IL-8、肿瘤坏死因子α-、、粒细胞集落刺激因子、粒-巨噬细胞集落刺激因子)。