IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.
IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.
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IFN-α1,8 抑制小鼠血管肉瘤中肿瘤诱导的血管生成。
DOI：
10.1089/jir.2006.26.353
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Lindner,DanielJ
中科院分区：
文献类型：
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作者：
Taylor,KevinL;Oates,RhondaK;Grane,Ron;Leaman,DouglasW;Borden,ErnestC;Lindner,DanielJ
Interferon-α(IFN-α) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomasin vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-α1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferationin vitroby 40% at 103U/mL (p= 0.028).In vivo,IFN-α1,8 inhibited SVR tumor volume by 71% (p= 0.047) and MS1-VEGF volume by 79% (p= 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p= 0.005) and in MS1-VEGF tumors by 58% (p= 0.001). Sera from IFN-α1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p= 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-α1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p< 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p= 0.001). Given the magnitude of thein vivoresponse, these data suggested that the antitumor effects of IFN-α1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.
