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Studies on Structure, Function and Metastasis of Abnormal Fibronectin fragment in Cancer Diseases.

癌症疾病中纤连蛋白异常片段的结构、功能和转移研究。

基本信息

批准号：
01570769
负责人：
TAKATSUKA Jun
金额：
$ 1.28万
依托单位：
Toho University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Extracellular matrix protein, of which fibronectin (FN) is representative, extensively exists in cellular basement membrane and interstitium, adheres and fixes the cells, and arranges orderly many cells and maintain the preservation of the tissue texture and the uniqueness of textural function in the living tissue. In FN molecules the part of the cell adhesive activity is cell binding domain which is nearly center of FN molecules, because this part adheres and fixes the cells and becomes, in a sense, an anchor of the cells, most cells locate in the same region through life and play their given roles. However carcinoma cell evades the preservation of the cell and the controle of the normal tissue, transfers to various sites in the body, and metastasis.We have determined FN in the urine of the patients with various gastrointestinal carcinomas and reported the observation that in most carcinomas FN increased as the carcinoma developed and FN remarkably increased in the case of metastasis. … More FN in the urine of the patients with gastrointestinal carcinomas was refined and its structure and function was studied, as a result of that it has become clear that 100kDa by molecule weight of FN fragments, which was not found in benign disease of many gastrointestinal carcinomas such as gastric cancer, colon cancer, rectum cancer, and liver cancer, were excreted into the urine. These fragments were also confirmed to be the fragments centering around cell binding domain.When carcinoma tissue was immunohistochemically studied, the stained features with polyclonal antibody showed FN distribution in interstitium and basement membrane of carcinoma tissue, but the stained features with monoclonal antibody which was specific to domain of FN showed discontinuity and inequality of FN distribution in interstitium and basement membrane. That was thought that carcinoma cell broke cell binding domain of FN existing in cellular interstitium and bacement membrane. Then it was suggested that carcinoma cell, which possessed characteristic property as metastasis, destroyed and broke cell binding domain of FN coiling round and activating as an anchor. It was thought that the fact that cell binding domain remarkably increased in the urine in the case of metastasis resulted from taking off the anchor. We want to further study for making clear the mechanism of metastasis. Less

以纤维连接蛋白（FN）为代表的细胞外基质蛋白广泛存在于细胞的基底膜和结缔组织中，粘附固定细胞，使许多细胞排列有序，维持活组织中组织质地的保存和组织功能的独特性。在FN分子中，细胞粘附活性的部分是细胞结合结构域，它几乎是FN分子的中心，因为该部分粘附和固定细胞，在某种意义上成为细胞的锚，大多数细胞一生都位于同一区域并发挥其特定的作用。但癌细胞逃避了正常组织的控制和细胞的保存，转移到身体的各个部位，发生转移，我们测定了各种消化道肿瘤病人尿中的FN，发现大多数肿瘤随着肿瘤的发展FN增高，转移时FN明显增高。 ...更多信息对胃肠道癌患者尿中的FN进行了提纯，并对其结构和功能进行了研究，结果表明，在胃肠道癌的良性疾病如胃癌、结肠癌、直肠癌和肝癌中未发现的分子量为100kDa的FN片段被排泄到尿中。对癌组织进行免疫组化染色时，多克隆抗体的染色特征显示FN分布于癌组织的基底膜和结缔组织中，而针对FN结构域的单克隆抗体的染色特征显示FN分布于癌组织的基底膜和结缔组织中的不连续性和不均匀性。认为癌细胞破坏了存在于细胞壁和细胞膜上的FN的细胞结合域。提示具有转移特性的癌细胞破坏并断裂了FN的细胞结合域，使其卷曲成一个锚而激活。据认为，在转移的情况下，尿中细胞结合结构域显著增加的事实是由于除去了锚。我们希望通过进一步的研究来阐明肿瘤转移的机制。少