Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy
Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy
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DOI：
10.1096/fj.01-0813com
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发表时间：
2002-09-01
期刊：
影响因子：
4.8
通讯作者：
D'Amato, RJ
中科院分区：
文献类型：
--
作者：
Udagawa, T;Fernandez, A;D'Amato, RJ
一些人类肿瘤系在接种到免疫抑制小鼠体内时不会形成可见的肿瘤。在将它们接种到小鼠体内之前，通过用绿色荧光蛋白转染它们来追踪这些人类肿瘤系的命运。尽管肿瘤系未能逐渐生长，但它们形成了通过平衡增殖和凋亡维持恒定质量的小型休眠微观病灶。用 VEGF(165) 或激活的 c-Ha-ras 转染细胞会诱导休眠丧失，这与血管生成平衡向血管分布增加和肿瘤细胞凋亡减少的方向转变相关。这些结果支持了一种模型，其中休眠的丧失部分是通过向血管生成表型的转变来控制的。这些肿瘤系可以作为研究控制休眠的细胞机制和识别促进失去平衡增殖和凋亡的因素的模型。最后，这些模型可能有助于设计和测试旨在根除休眠肿瘤和预防肿瘤复发的疗法。
Some human tumor lines do not form visible tumors when inoculated into immunosuppressed mice. The fate of these human tumor lines was followed by transfecting them with green fluorescence protein before inoculating them into mice. Although the tumor lines failed to grow progressively, they formed small dormant microscopic foci maintained at constant mass by balanced proliferation and apoptosis. Transfecting the cells with either VEGF(165) or activated c-Ha-ras induced loss of dormancy, which correlated with a shift in the angiogenic balance toward increased vascularity with reduced tumor cell apoptosis. These results support a model in which loss of dormancy is controlled in part by a switch to an angiogenic phenotype. These tumor lines may serve as models for investigating the cellular mechanisms controlling dormancy and identifying those factors that promote the loss of balanced proliferation and apoptosis. Finally, these models may prove useful in the design and testing of therapies directed toward eradicating dormant tumors and preventing tumor recurrence.