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两种源自可移植大鼠恶性纤维组织细胞瘤建立的不同克隆细胞系所诱导肿瘤中血管内皮生长因子和碱性成纤维细胞生长因子的表达

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.

作者信息

Tsunenari I, Yamate J, Sharma K D, Kawachi M, Sakuma S

机构信息

Department of Toxicology and Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Hyogo, Japan.

出版信息

J Vet Med Sci. 2000 Jul;62(7):699-705. doi: 10.1292/jvms.62.699.

Abstract

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.

摘要

为了建立间充质肿瘤发生过程中血管生成因子的基线数据,采用免疫组织化学和蛋白质印迹法,对源自F344大鼠可移植性恶性纤维组织细胞瘤(MFH)的植入性MT-8和MT-9肿瘤中血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的表达进行了研究。通过植入肿瘤组织片段,在同基因大鼠中培养MT-8和MT-9肿瘤。在植入后(PI)第3、6、9和17天检查MT-8肿瘤,在PI第9、14、17和23天检查MT-9肿瘤。MT-8肿瘤的生长速度比MT-9肿瘤快。组织学上,MT-8肿瘤具有未分化肉瘤的特征,而MT-9肿瘤呈现MFH典型的席纹状生长模式。免疫组织化学检测显示,构成MT-8和MT-9肿瘤的所有细胞均与VEGF和bFGF抗体发生反应,表明这些因子由间充质肿瘤细胞产生。然而,在所检查的肿瘤之间,这些免疫反应没有明显差异。因此,对蛋白质印迹法获得的条带进行光密度扫描。MT-8肿瘤中VEGF和bFGF的表达水平在PI第3天至9天逐渐升高,MT-9肿瘤中在PI第9天至17天逐渐升高。在最后检查日,两种肿瘤中bFGF的水平以及MT-9肿瘤中VEGF的水平均下降,但MT-8肿瘤中VEGF的表达水平仍在升高。这些发现表明,VEGF和bFGF可能在间充质肿瘤发生早期的血管生成过程中协同发挥作用。

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