The hypoxic response of tumors is dependent on their microenvironment
The hypoxic response of tumors is dependent on their microenvironment
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DOI：
10.1016/s1535-6108(03)00194-6
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发表时间：
2003-08-01
期刊：
影响因子：
50.3
通讯作者：
Bergers, G
中科院分区：
文献类型：
--
作者：
Blouw, B;Song, HQ;Bergers, G
为了揭示低氧和血管生成在星形细胞瘤进展中的功能意义，我们从小鼠原代星形胶质细胞中获得了基因工程转化的星形胶质细胞，并删除了低氧反应转录因子HIF-1α或其靶基因血管生成因子VEGF。在缺乏血管的皮下环境中，HIF-1α和VIEGF缺陷转化的星形胶质细胞的生长会导致严重的坏死、生长减少和血管密度，而当相同的细胞被放置在血管丰富的脑实质中时，HIF-1α基因敲除的肿瘤的生长被逆转，但不是VEGF基因敲除的肿瘤：HIF-1α基因缺陷的肿瘤生长更快，并更快和更广泛地渗透到大脑。这些结果表明，HIF-1α在肿瘤进展中具有不同的作用，这在很大程度上依赖于肿瘤现有的微环境。
To reveal the functional significance of hypoxia and angiogenesis in astrocytoma progression, we created genetically engineered transformed astrocytes from murine primary astrocytes and deleted the hypoxia-responsive transcription factor HIF-1alpha or its target gene, the angiogenic factor VEGF. Growth of HIF-1alpha- and VIEGF-deficient transformed astrocytes in the vessel-poor subcutaneous environment results in severe necrosis, reduced growth, and vessel density, whereas when the same cells are placed in the vascular-rich brain parenchyma, the growth of HIF-1alpha knockout, but not VEGF knockout tumors, is reversed: tumors deficient in HIF-1alpha grow faster, and penetrate the brain more rapidly and extensively. These results demonstrate that HIF-1alpha has differential roles in tumor progression, which are greatly dependent on the extant microenvironment of the tumor.