Analysis of cancer metastasis to lymphnodes through lymphocyte adhesion molea

近年来，肿瘤淋巴结转移的发生被认为需要肿瘤细胞与淋巴基质细胞之间的直接粘附作用。本研究的重点是粘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细胞在基质细胞的细胞质下爬行。我们通过分别用Jurkat和Molt-4淋巴瘤细胞免疫大鼠来产生单克隆抗体DG-20和DG-64。Mab DG-20或DG-64特异性抑制这些淋巴瘤细胞与基质的结合。在该实验中，还需要在啮齿动物模型中建立具有转移至淋巴结或远端器官的倾向的人肿瘤细胞系。为此，我们建立了人甲状腺癌细胞系TA-K、TA-N、TA-M和TA-G，这些细胞系经病理学标准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，所有细胞系中sialyl Lex的高表达，所有细胞系中没有E-cadherin或α-catenin的表达。β-catenin在TA-K、TA-N和TA-M中呈阳性表达，在TA-G中呈弱阳性表达，免疫组化显示DG-20和DG-64呈弱阳性表达。对细胞因子的体外产生进行了检测。在每个细胞系中产生各种细胞因子（IL-1、IL-2、IL-6、IL-7、IL-8、TNF α、G-CSF、GM-CSF）。

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.