Expression of vascular endothelial growth factor in a human hemangiosarcoma cell line (ISO-HAS)

Expression of vascular endothelial growth factor in a human hemangiosarcoma cell line (ISO-HAS)
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DOI:
10.1007/s004030100228
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发表时间:
2001-06-01
影响因子:
3
通讯作者:
Katsuoka, K
Katsuoka, K
中科院分区:
医学3区
文献类型:
--
作者:
Amo, Y;Masuzawa, M;Katsuoka, K

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血管内皮生长因子(VEGF)除了在体外是内皮细胞的特异性促分裂原之外,还已知在体内诱导血管生成。这些功能提示VEGF可能在血管瘤的生长中起重要作用。以往的研究已通过免疫组织化学染色和原位杂交证实血管肉瘤中VEGF及其受体flt-1或KDR/flk-1的表达。本研究证实血管肉瘤细胞系ISO-HAS表达VEGF及其两种受体flt-1和KDR的mRNA,并分泌VEGF蛋白。发现佛波醇12-肉豆蔻酸酯13-乙酸酯可增强VEGF mRNA表达和蛋白分泌。此外,我们证明ISO-HAS细胞对重组人VEGF(165)有剂量依赖性的细胞增殖和生长上调反应。这些结果表明VEGF-VEGF受体系统在血管肉瘤细胞的增殖和生长中起作用。
Vascular endothelial growth factor (VEGF), in addition to being a specific mitogen of endothelial cells in vitro, is also known to induce angiogenesis in vivo. These functions suggest that VEGF may play an important role in the growth of hemangiosarcomas. Previous studies have demonstrated the expression of VEGF and its receptors, flt-1 or KDR/flk-1, in hemangiosarcomas by immunohistochemical staining and in situ hybridization, In the present study, however, we demonstrated that tumor cells of the hemangiosarcoma cell line ISO-HAS express mRNA of VEGF and its two receptors, flt-1 and KDR, and secrete VEGF protein. VEGF mRNA expression and protein secretion were found to be enhanced by phorbol 12-myristate 13-acetate, In addition, we demonstrated that ISO-HAS cells respond to recombinant human VEGF(165) with a dose-dependent up-regulation of cell proliferation and growth. These results suggest that the VEGF-VEGF receptor system plays a role in proliferation and growth of hemangiosarcoma cells.