Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy.
Nuffield Division of Laboratory Science, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX39DU, UK.
Cells. 2021 Mar 13;10(3):639. doi: 10.3390/cells10030639.
Angiogenesis is a crucial event in the physiological processes of embryogenesis and wound healing. During malignant transformation, dysregulation of angiogenesis leads to the formation of a vascular network of tumor-associated capillaries promoting survival and proliferation of the tumor cells. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. Over this period numerous authors published data of vascularization of tumors, which attributed the cause of neo-vascularization to various factors including inflammation, release of angiogenic cytokines, vasodilatation, and increased tumor metabolism. More recently, it has been demonstrated that tumor vasculature is not necessarily derived by endothelial cell proliferation and sprouting of new capillaries, but alternative vascularization mechanisms have been described, namely vascular co-option and vasculogenic mimicry. In this article, we have analyzed the mechanisms involved in tumor vascularization in association with classical angiogenesis, including post-natal vasculogenesis, intussusceptive microvascular growth, vascular co-option, and vasculogenic mimicry. We have also discussed the role of these alternative mechanism in resistance to anti-angiogenic therapy and potential therapeutic approaches to overcome resistance.
血管生成是胚胎发生和创伤愈合等生理过程中的关键事件。在恶性转化过程中，血管生成的失调会导致肿瘤相关毛细血管的血管网络形成，从而促进肿瘤细胞的存活和增殖。从 Judah Folkman 提出的肿瘤生长依赖血管生成的假设开始，该研究领域有坚实的科学基础，并且抑制血管生成是治疗癌症的治疗开发的主要领域。在此期间，许多作者发表了肿瘤血管生成的数据，这些数据将新血管生成的原因归因于多种因素，包括炎症、血管生成细胞因子的释放、血管扩张和肿瘤代谢增加。最近，已经证明肿瘤脉管系统不一定来源于内皮细胞的增殖和新毛细血管的发芽，而是已经描述了替代性的血管生成机制，即血管选择和血管生成拟态。在本文中，我们分析了与经典血管生成相关的肿瘤血管生成的机制，包括出生后血管生成、间位微血管生长、血管选择和血管生成拟态。我们还讨论了这些替代机制在抗血管生成治疗中的耐药性中的作用以及克服耐药性的潜在治疗方法。
