INDUCTION OF ANGIOGENESIS DURING THE TRANSITION FROM HYPERPLASIA TO NEOPLASIA
INDUCTION OF ANGIOGENESIS DURING THE TRANSITION FROM HYPERPLASIA TO NEOPLASIA
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DOI：
10.1038/339058a0
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发表时间：
1989-05-04
期刊：
影响因子：
64.8
通讯作者：
HANAHAN, D
中科院分区：
文献类型：
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作者：
FOLKMAN, J;WATSON, K;HANAHAN, D
现在已经确定肿瘤的无限制生长依赖于血管生成1,2。然而，先前关于肿瘤生长的研究并没有揭示在早期肿瘤发展过程中何时或如何过渡到血管生成状态。携带致癌基因的转基因小鼠的出现可重复地诱发特定细胞类型的肿瘤3 - 6，为研究多步骤肿瘤发生提供了一种新的形式7,8。在其中一种模型中，在胰岛β细胞中表达致癌基因的转基因小鼠遗传地再现了从正常到增生再到肿瘤的过程6。我们在此报告，血管生成活性首先出现在肿瘤形成之前的增生性胰岛的一个子集。一项新的体外测定证实了增生性细胞并不会导致血管生成。相反，一些增生性胰岛在体内新生血管形成时，其频率与随后的肿瘤发病率密切相关，从而成为体外血管生成素。这些发现表明，诱导血管生成是癌变的重要步骤。
IT is now well established that unrestricted growth of tumours is dependent upon angiogenesis1,2. Previous studies on tumour growth, however, have not revealed when or how the transition to an angiogenic state occurs during early tumour development. The advent of transgenic mice carrying oncogenes that reproducibly elicit tumours of specific cell types3–6is providing a new format for studying multi-step tumorigenesis7,8. In one of these models, transgenic mice expressing an oncogene in the β-cells of the pancreatic islets heritably recapitulate a progression from normality to hyperplasia to neoplasia6. We report here that angiogenic activity first appears in a subset of hyperplastic islets before the onset of tumour formation. A novelin vitroassay confirms that hyperplasiaper sedoes not obligate angiogenesis. Rather, a few hyperplastic islets become angiogenicin vitroat a time when such islets are neovascularizedin vivoand at a frequency that correlates closely with subsequent tumour incidence. These findings suggest that induction of angiogenesis is an important step in carcinogenesis.