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

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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