Inhibition of tumor growth by a truncated and soluble form of melanotransferrin
Inhibition of tumor growth by a truncated and soluble form of melanotransferrin
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DOI：
10.1016/j.yexcr.2007.04.013
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发表时间：
2007-08-01
影响因子：
3.7
通讯作者：
Beliveau, Richard
中科院分区：
文献类型：
--
作者：
Rolland, Yanneve;Demeule, Michel;Beliveau, Richard
黑转铁蛋白是一种在细胞膜上表达并在细胞外环境中分泌的糖蛋白。据报道，重组截断形式的膜结合黑素转铁蛋白（sMTf）具有体外抗血管生成特性。在这里，我们表明sMTf处理导致50%的新生血管抑制在基质（TM）植入物受到生长因子的刺激。利用胶质母细胞瘤异种移植模型，我们证明了微渗透泵以2.5 mg/kg/天和10 mg/kg/天递送sMTf分别抑制肿瘤生长73%和91%。在肺癌异种移植模型中，每天2.5和10 mg/kg的sMTf治疗对肿瘤生长的抑制作用分别为87%和97%。此外，10 mg/kg/天的sMTf治疗小鼠皮下胶质母细胞瘤和肺癌肿瘤在研究中没有明显的生长。与内啡肽mRNA表达减少相关，smtf治疗的胶质母细胞瘤中血红蛋白含量减少了一半。体外实验显示，sMTf处理的NCI-H460细胞的侵袭能力受到抑制，同时低密度脂蛋白受体蛋白和尿激酶纤溶酶原激活物受体的表达减少。总之，我们的研究结果表明，sMTf具有抗癌和抗血管生成活性，表明其施用可能为治疗癌症提供新的治疗策略。(c) 2007爱思唯尔公司版权所有。
Melanotransferrin is a glycoprotein expressed at the cell membrane and secreted in the extracellular environment. Recombinant truncated form of membrane-bound melanotransferrin (sMTf) was reported to exert in vitro anti-angiogenic properties. Here we show that sMTf treatment leads to a 50% inhibition of neovascularization in Matrigel (TM) implants when stimulated by growth factors. Using a glioblastoma xenograft model, we demonstrate that sMTf delivery at 2.5 and 10 mg/kg/day by micro-osmotic pump inhibits tumor growth by 73% and 91%, respectively. In a lung carcinoma xenograft model, sMTf treatment at 2.5 and 10 mg/kg/day impeded tumor growth by 87% and 97%. Furthermore, subcutaneous glioblastoma and lung carcinoma tumors from mice treated with 10 mg/kg/day of sMTf present insignificant growth toward the study. In association with a reduction in endoglin mRNA expression, the hemoglobin content decreased by half in sMTf-treated glioblastoma tumors. In vitro experiments revealed that NCI-H460 cells treated with sMTf display an inhibition in their invasive capabilities with a concomitant reduction in the expression of the low-density lipoprotein receptor protein and urokinase plasminogen activator receptor. Altogether, our results demonstrate that sMTf exerts anti-cancer and anti-angiogenic activities, suggesting that its administration may provide novel therapeutic strategies for the treatment of cancer. (c) 2007 Elsevier Inc. All rights reserved.