Ribatti D, Nico B, Crivellato E, Roccaro A M, Vacca A
Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy.
Leukemia. 2007 Jan;21(1):44-52. doi: 10.1038/sj.leu.2404402. Epub 2006 Sep 21.
Spontaneously arising tumor cells are not usually angiogenic at first. The phenotypic switch to angiogenesis is usually accomplished by a substet that induces new capillaries that then converge toward the tumor. The switch clearly involves more than simple upregulation of angiogenic activity and is thought to be the result of a net balance of positive and negative regulators. Tumor growth is although to require disruption of this balance and hence this switch must turned on for cancer progression. Progenitor endothelial cells, the crosstalk between angiogenic factors and their receptors and the interaction between vasculogenesis and lymphangiogenesis are all factors that may contribute to the switch. Its promotion is also the outcome of genetic instability resulting in the emergence of tumor cell lines. This review describes the history of the angiogenic switch illustrated in the literature and with particular reference to the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human papilloma virus) HPV16 and papilloma virus, used for stage-specific assessment of the effects of antiangiogenic and antitumorigenic agents.
自发产生的肿瘤细胞起初通常不具有血管生成能力。向血管生成的表型转变通常由一个亚群完成，该亚群诱导新的毛细血管向肿瘤汇聚。这种转变显然不仅仅涉及血管生成活性的简单上调，被认为是正负调节因子净平衡的结果。肿瘤生长被认为需要打破这种平衡，因此这种转变必须开启才能实现癌症进展。祖细胞内皮细胞、血管生成因子与其受体之间的相互作用以及血管生成与淋巴管生成之间的相互作用都是可能促成这种转变的因素。其促进也是遗传不稳定导致肿瘤细胞系出现的结果。本综述描述了文献中阐述的血管生成转变的历史，并特别提及了三种转基因小鼠模型，即RIP1-TAG2、角蛋白-14（K14）（人乳头瘤病毒）HPV16和乳头瘤病毒，用于对抗血管生成和抗肿瘤药物效果进行阶段特异性评估。
