Therapeutic Application of Brain-Specific Angiogenesis Inhibitor 1 for Cancer Therapy.
Therapeutic Application of Brain-Specific Angiogenesis Inhibitor 1 for Cancer Therapy.
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DOI：
10.3390/cancers13143562
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发表时间：
2021-07-16
期刊：
影响因子：
5.2
通讯作者：
Yoo JY
中科院分区：
文献类型：
--
作者：
Nair M;Bolyard C;Lee TJ;Kaur B;Yoo JY
脑特异性血管生成抑制剂1 （Brain-specific angiogenesis inhibitor 1, BAI1）是一种跨膜粘附GPCR蛋白，在许多细胞过程和功能中起重要作用。BAI1促进抗肿瘤和抗血管生成作用的能力已被探索和发展为几种不同恶性肿瘤的治疗选择。在这里，我们详细介绍了BAI的系统概述，重点是它对癌症的治疗潜力。鉴于近年来溶瘤病毒和基因治疗在针对各种类型癌症方面的发展，我们的综述文章与临床翻译高度相关。脑特异性血管生成抑制剂1 （Brain-specific angiogenesis inhibitor 1, BAI1/ADGRB1）是一种粘附G蛋白偶联受体，在吞噬、炎症、突触发生、血管生成抑制和成肌细胞融合中发挥关键作用。顾名思义，它主要在大脑中表达，在正常成人和发育中的大脑中表达量很高。此外，它在脑癌，如胶质母细胞瘤（GBM）和外周肿瘤中的表达减少，表明BAI1是一种肿瘤抑制基因。一些研究人员已经证明，恢复癌细胞中BAI1的表达会导致肿瘤生长和血管生成的减少。它的表达也被证明与肿瘤进展、新血管形成和肿瘤周围脑水肿呈负相关。恢复BAI1表达的一种方法是使用溶瘤病毒（OV）治疗，这一策略已在各种肿瘤模型中进行了测试。经工程改造表达BAI1分泌片段的溶瘤性单纯疱疹病毒，称为血管抑制素（Vstat120），在多种肿瘤模型中显示出强大的抗肿瘤和抗血管生成作用。在体外和体内模型中，表达vstat120的oHSVs与其他化疗药物联合使用也显示出总体抗肿瘤疗效的提高。现就BAI1的结构和功能进行综述，并对其在肿瘤治疗中的应用进行综述。
Brain-specific angiogenesis inhibitor 1 (BAI1) is a transmembrane adhesion GPCR protein that plays an important role in many cellular processes and functions. The ability of BAI1 to promote anti-tumor and anti-angiogenic effects has been explored and developed as a treatment option for several different malignancies. Here, we have detailed a systemic overview of BAI, with a focus on its therapeutic potential for cancer. Due to the recent developments in oncolytic viruses and gene therapeutics towards targeting various types of cancers, our review article is highly relevant to clinical translation. Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1) is an adhesion G protein-coupled receptor that has been found to play key roles in phagocytosis, inflammation, synaptogenesis, the inhibition of angiogenesis, and myoblast fusion. As the name suggests, it is primarily expressed in the brain, with a high expression in the normal adult and developing brain. Additionally, its expression is reduced in brain cancers, such as glioblastoma (GBM) and peripheral cancers, suggesting that BAI1 is a tumor suppressor gene. Several investigators have demonstrated that the restoration of BAI1 expression in cancer cells results in reduced tumor growth and angiogenesis. Its expression has also been shown to be inversely correlated with tumor progression, neovascularization, and peri-tumoral brain edema. One method of restoring BAI1 expression is by using oncolytic virus (OV) therapy, a strategy which has been tested in various tumor models. Oncolytic herpes simplex viruses engineered to express the secreted fragment of BAI1, called Vasculostatin (Vstat120), have shown potent anti-tumor and anti-angiogenic effects in multiple tumor models. Combining Vstat120-expressing oHSVs with other chemotherapeutic agents has also shown to increase the overall anti-tumor efficacy in both in vitro and in vivo models. In the current review, we describe the structure and function of BAI1 and summarize its application in the context of cancer treatment.
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发表时间：
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期刊：
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影响因子：
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