Expressions of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor in Tumors Induced by Two Different Cloned Cell Lines Established from Transplantable Rat Malignant Fibrous Histiocytoma.

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  • TSUNENARI Ichiro
    Department of Toxicology and Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd.
  • YAMATE Jyoji
    Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University
  • D. SHARMA Kailash
    Department of Toxicology and Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd.
  • KAWACHI Mamoru
    Department of Toxicology and Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd.
  • SAKUMA Sadashige
    Department of Veterinary Pathology, College of Agriculture, Osaka Prefecture University

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In order to establish base-line data on angiogenic factors in development of mesenchymal tumors, expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in implanted MT-8 and MT-9 tumors, both derived from a transplantable malignant fibrous histiocytoma (MFH) in the F344 rat, were investigated by immunohistochemistry and Western blotting method. MT-8 and MT-9 tumors were developed in syngeneic rats by implant of a tumor tissue fragment. MT-8 tumors were examined on post-implantation (PI) days 3, 6, 9 and 17, and MT-9 tumors were on PI days 9, 14, 17 and 23. The growth of MT-8 tumors was faster than that of MT-9 tumors. Histologically, MT-8 tumors were features of undifferentiated sarcomas, whereas MT-9 tumors exhibited a typical storiform growth pattern of MFH. Immunohistochemically, all cells constituting MT-8 and MT-9 tumors reacted with antibodies to VEGF and bFGF, indicating production of these factors by mesenchymal neoplastic cells. However, there were no marked differences in these immunoreactions between tumors examined. Thus, the bands obtained in the Western blotting methods were densitometrically scanned. The expression levels of VEGF and bFGF gradually increased PI day 3 to 9 in MT-8 tumors and PI day 9 to 17 in MT-9 tumors. On last examination day, the levels of bFGF in both tumors and of VEGF in MT-9 tumors decreased, but the VEGF expression level in MT-8 tumors was still increased. These findings indicated that VEGF and bFGF may contribute cooperatively to angiogenesis in an early growth of mesenchymal tumor development.

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