Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis
Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis
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DOI：
10.1126/science.1150224
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发表时间：
2008-01-11
期刊：
影响因子：
56.9
通讯作者：
Mittal, Vivek
中科院分区：
文献类型：
--
作者：
Gao, Dingcheng;Nolan, Daniel J.;Mittal, Vivek
血管生成介导的微转移向致死性大转移的进展是癌症患者死亡的主要原因。在这里，使用小鼠肺转移模型，我们确定骨髓（BM）衍生的内皮祖细胞（EPCs）作为这种血管生成开关的关键调节因子。我们发现，肿瘤诱导转录因子Id1在EPCs中的表达，并且在转移定植后抑制Id1阻断了EPC动员，引起血管生成抑制，损害了肺大转移，并增加了荷瘤动物的存活率。这些发现确立了EPCs在临床前模型中转移进展中的作用，并表明选择性靶向EPCs可能值得研究作为肺转移癌症患者的治疗方法。
Angiogenesis- mediated progression of micrometastasis to lethal macrometastasis is the major cause of death in cancer patients. Here, using mouse models of pulmonary metastasis, we identify bone marrow ( BM)- derived endothelial progenitor cells ( EPCs) as critical regulators of this angiogenic switch. We show that tumors induce expression of the transcription factor Id1 in the EPCs and that suppression of Id1 after metastatic colonization blocked EPC mobilization, caused angiogenesis inhibition, impaired pulmonary macrometastases, and increased survival of tumor- bearing animals. These findings establish the role of EPCs in metastatic progression in preclinical models and suggest that selective targeting of EPCs may merit investigation as a therapy for cancer patients with lung metastases.