文章：

肿瘤发生和血管生成开关

Tumorigenesis and the angiogenic switch

原文发布日期：2003-06-01

DOI: 10.1038/nrc1093

类型: Review Article

开放获取: 否

要点：

1. Tumour heterogeneity leads to heterogeneity in the tumour vasculature. Just as there are multiple phenotypes for any given tumour type, so can there be multiple phenotypes of the tumour angiogenic process.
2. The onset of angiogenesis, or the 'angiogenic switch', is a discrete step that can occur at any stage of tumour progression. It depends on the type of tumour and its microenvironment.
3. Tumour angiogenesis differs significantly from physiological angiogenesis. Differences include aberrant vascular structure, altered endothelial-cell–pericyte interactions, abnormal blood flow, increased permeability and delayed maturation.
4. The abnormal features of the tumour vasculature are believed to result from the disproportionate expression of angiogenic cytokines and inhibitors. Expression of these varies from tumour to tumour.
5. Tumour hypoxia complicates the angiogenic response, depending on the status of p53, which can regulate key angiogenic cytokines and inhibitors.
6. The angiogenic activity of a tumour does not necessarily correlate with tumour aggressiveness. Nonetheless, it can be a prognostic factor for certain tumour types.
7. Anti-angiogenic agents can be used not only for the treatment of cancer, but also for the prevention of cancer recurrence or metastasis. Given the heterogeneity of tumour and blood-vessel growth, a multidrug approach that targets various factors might be more successful than monotherapy in restraining cancer growth.

要点翻译：

1. 肿瘤异质性导致肿瘤血管系统的异质性。正如任何给定肿瘤类型存在多种表型一样，肿瘤血管生成过程也可能存在多种表型。
2. 血管生成的发生，即"血管生成开关"，是一个离散步骤，可在肿瘤进展的任何阶段出现。这取决于肿瘤类型及其微环境。
3. 肿瘤血管生成与生理性血管生成显著不同。差异包括异常血管结构、改变的内皮细胞-周细胞相互作用、血流异常、通透性增加和成熟延迟。
4. 肿瘤血管系统的异常特征被认为是由血管生成细胞因子和抑制剂比例失调的表达所致。这些因子的表达因肿瘤而异。
5. 肿瘤缺氧使血管生成反应复杂化，其取决于p53的状态——该基因可调控关键血管生成细胞因子和抑制剂。
6. 肿瘤的血管生成活性未必与肿瘤侵袭性相关。然而，对于某些肿瘤类型而言，它可以作为预后因素。
7. 抗血管生成药物不仅可用于癌症治疗，还可用于预防癌症复发或转移。鉴于肿瘤和血管生长的异质性，针对多种因素的多药联合疗法可能比单药疗法更能有效抑制癌症生长。

英文摘要：

It has become evident that we cannot understand tumour growth without considering components of the stromal microenvironment, such as the vasculature. At the same time, the tumour phenotype determines the nature of the tumour vasculature. Much research is now devoted to determining the impact of angiogenesis on tumour development and progression, and the reciprocal influences of tumour products on the microvasculature. A more detailed understanding of the complex parameters that govern the interactions between the tumour and vascular compartments will help to improve anti-angiogenic strategies — not only for cancer treatment, but also for preventing recurrence.

摘要翻译： 

显而易见，若不考虑基质微环境的组分（如脉管系统），我们便无法理解肿瘤的生长。与此同时，肿瘤的表型又决定了其脉管系统的性质。目前，大量研究致力于阐明血管生成对肿瘤发生与进展的影响，以及肿瘤产物对微血管的反向作用。更深入地理解调控肿瘤与血管区室间相互作用的复杂参数，将有助于优化抗血管生成策略——不仅用于癌症治疗，也用于预防复发。

原文链接：

Tumorigenesis and the angiogenic switch