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

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基底膜和间质中，对细胞进行黏附和固定，使许多细胞有序排列，维持活组织中组织结构的保存和组织结构功能的独特性。在FN分子中，细胞黏附活性的一部分是细胞结合域，它几乎是FN分子的中心，因为这部分黏附和固定细胞，从某种意义上说，成为细胞的锚，大多数细胞在整个生命过程中都位于同一区域，并发挥其特定的作用。然而癌细胞逃避细胞的保存和正常组织的控制，转移到体内的不同部位，发生转移。我们测定了各种胃肠道肿瘤患者尿液中的Fn，发现在大多数肿瘤中，Fn随着肿瘤的发展而增加，在转移的情况下，Fn显著增加。…对胃肠道肿瘤患者尿液中Fn进行了进一步提纯，并对其结构和功能进行了研究。结果表明，许多胃肠道肿瘤如胃癌、结肠癌、直肠癌、肝癌等良性疾病中均有100 kDa的Fn片段排入尿液。免疫组织化学染色结果显示，多克隆抗体染色显示FN分布于癌组织的间质和基底膜，而针对FN区域的单抗染色特征显示FN在间质和基底膜的分布不连续和不均匀。认为癌细胞破坏了存在于细胞间质和基质膜中的FN的细胞结合域。由此推测，具有转移特性的癌细胞破坏和破坏了FN的细胞结合域，并以锚的形式被激活。有人认为，在转移的情况下，尿液中的细胞结合域显著增加，这是由于脱锚造成的。我们希望进一步研究肿瘤转移的机制。较少

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