Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), Department of Bioengineering, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu, India.
Centre for Biotechnology, Anna University, Chennai 600 025, Tamil Nadu, India.
Life Sci. 2020 Jul 1;252:117670. doi: 10.1016/j.lfs.2020.117670. Epub 2020 Apr 13.
Deregulation of angiogenesis is a key reason for tumor growth and progression. Several anti-angiogenic drugs in clinical practice attempt to normalize abnormal tumor vasculature. Unfortunately, these drugs are ineffective due to the development of resistance in patients after drug holidays. A sizable literature suggests that resistance to these anti-angiogenic drugs occurs due to various compensatory mechanisms of tumor angiogenesis. Therefore, we describe different compensatory mechanisms of tumor angiogenesis, and explain why intussusceptive angiogenesis (IA), is a crucial mechanism of compensatory angiogenesis in tumors which resist anti-VEGF (vascular endothelial growth factor) therapies. IA is often overlooked due to the scarcity of experimental models. Therefore, we examine data from existing experimental models and our novel ex-ovo model of angiogenesis in chick embryos, and explain the important genes and signaling pathways driving IA. Using bio-informatic analyses of major genes regulating conventional sprouting angiogenesis (SA) and intussusceptive angiogenesis, we provide fresh insights on the 'angiogenic switch' which regulates the transition from SA to IA. Finally, we examine the interplay between molecules regulating SA, IA, and molecules known to promote tumor progression. Based on these analyses, we conclude that intussusceptive angiogenesis (IA) is a promising therapeutic target for developing effective anti-cancer treatment regimes.
血管生成的失调是肿瘤生长和进展的一个关键原因。几种临床实践中的抗血管生成药物试图使异常的肿瘤血管正常化。不幸的是，由于药物停药后患者产生耐药性，这些药物无效。大量文献表明，这些抗血管生成药物的耐药性是由于肿瘤血管生成的各种代偿机制引起的。因此，我们描述了肿瘤血管生成的不同代偿机制，并解释了为什么在抗 VEGF（血管内皮生长因子）治疗的肿瘤中，内陷性血管生成（IA）是肿瘤代偿性血管生成的关键机制。由于实验模型的缺乏，IA 经常被忽视。因此，我们检查了来自现有实验模型和我们在鸡胚中新颖的体外血管生成模型的数据，并解释了驱动 IA 的重要基因和信号通路。我们通过对调节常规发芽血管生成（SA）和内陷性血管生成的主要基因的生物信息学分析，提供了关于调节从 SA 到 IA 转变的“血管生成开关”的新见解。最后，我们研究了调节 SA、IA 的分子与已知促进肿瘤进展的分子之间的相互作用。基于这些分析，我们得出结论，内陷性血管生成（IA）是开发有效抗癌治疗方案的有前途的治疗靶点。
