口腔癌におけるフィブロネクチンおよびフィブリノーゲンの動態に関する実験的研究

Abstract

Fibronectin (FN), one of the glycoproteins existing in plasma and extracellular matrix, is found in the connective tissue stroma and basement membrane of cancer. It is also reported that fibrinogen (Fbg) cross-links to FN deposited in the tumor stroma and shows a high serum level in cancer patients. The purpose of this study was to examine the tissue localization and distribution of FN and Fbg with time lapse in experimentally induced carcinoma (VX2 carcinoma implanted in tongue) and its metastatic lesions in rabbits and to compare with those observed in wound healing process of normal oral mucosa in rabbits.Distribution of FN and Fbg was examined with direct imrnunoperoxidase technique. The plasma FN and Fbg levels in rabbits bearing VX2 carcinoma and foreign body granuloma were also quantitatively measured by a single radial immunodiffusion method.The results obtained were as follows:1) The tumor enlarged aggresively, and metastasized to cervical lymph nodes and lungs on 10 days after implantation.2) FN deposits were found in the tumor stroma on 7 days after implantation and in a capsulelike connective tissue around the tumor nest on 14 days after.3) Fbg was present as a fibrin nets surrounding the tumor nest on 7 days after implantation and it disappeared after 10-14 days.4) In the metastatic tissues (cervical lymph nodes' and lungs), FN and Fbg showed no marked deposits except around the tumor cells in the early stage of metastasis.5) In the experimentally induced wound of oral mucosa, FN and Fbg deposits were consistent with the distribution of fibroblast, collagen fiber, and histiocyte in immature granulation tissue. This reaction was similar to that observed in stroma of early VX2 carcinoma.6) The plasma FN level in rabbits bearing VX2 carcinoma increased gradually in 26% on 21 days after implantation comparing with the control value. The plasma Fbg also showed increased levels in 68% on 28 days after implantation comparing with the control value.The results suggested that the stromal fibroid production in malignant tumors might be one of the vital defense reactions against tumor growth similar to the case of wound healing reactions. It is also suggested that the tissue distribution of FN and Fbg as well as plasma FN and Fbg levels would be a good biological marker of tumor growth and metastatic process in oral cancers.