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

以纤连蛋白（FN）为代表的细胞外基质蛋白广泛存在于细胞基膜和间质中，粘附和固定细胞，使许多细胞有序排列，维持活组织中组织肌理的保存和肌理功能的独特性。在FN分子中，细胞粘附活性的部分是靠近FN分子中心的细胞结合域，因为这部分粘附和固定细胞，在某种意义上成为细胞的锚点，大多数细胞一生都位于同一区域，发挥其既定的作用。然而，癌细胞逃避了细胞的保存和正常组织的控制，转移到身体的各个部位，并转移。我们测定了各种胃肠道癌患者尿液中的FN，并报道了在大多数癌中FN随着癌的发展而增加，在转移的情况下FN显著增加。…对胃肠道癌患者尿液中更多的FN进行了细化，并对其结构和功能进行了研究，明确了在胃癌、结肠癌、直肠癌、肝癌等许多胃肠道癌的良性疾病中没有发现的按分子量计算的100kDa的FN片段排泄到尿液中。这些片段也被证实是围绕细胞结合域的片段。对癌组织进行免疫组织化学染色时，多克隆抗体染色特征显示癌组织间质和基底膜中FN分布，而FN特异结构域单克隆抗体染色特征显示间质和基底膜中FN分布不连续、不均匀。认为癌细胞破坏了存在于细胞间质和细胞膜上的FN结合域。结果表明，具有转移特性的癌细胞破坏并破坏了FN的结合结构域，该结构域盘绕并作为锚点激活。人们认为，在转移的情况下，尿液中细胞结合域的显著增加是由于脱去锚定的结果。我们希望进一步研究以明确其转移机制。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