Olsen Jun Jun, Pohl Sebastian Öther-Gee, Deshmukh Abhijeet, Visweswaran Malini, Ward Natalie C, Arfuso Frank, Agostino Mark, Dharmarajan Arun
The School of Human Sciences, The University of Western Australia, Nedlands, WA.
Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Bentley, WA.
Clin Biochem Rev. 2017 Nov;38(3):131-142.
Angiogenesis is a normal biological process wherein new blood vessels form from the growth of pre-existing blood vessels. Preventing angiogenesis in solid tumours by targeting pro-angiogenic factors including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), basic fibroblast growth factor (bFGF), hepatocyte growth factor, and platelet-derived growth factor (PDGF) is currently under investigation for cancer treatment. Concurrently targeting the cell signalling pathways involved in the transcriptional and post-translational regulation of these factors may provide positive therapeutic results. One such pathway is the Wnt signalling pathway. Wnt was first discovered in mice infected with mouse mammary tumour virus, and has been crucial in improving our understanding of oncogenesis and development. In this review, we summarise molecular and cellular aspects of the importance of Wnt signalling to angiogenesis, including β-catenin-dependent mechanisms of angiogenic promotion, as well as the study of Wnt antagonists, such as the secreted frizzled-related protein family (SFRPs) which have been shown to inhibit angiogenesis. The growing understanding of the underlying complexity of the biochemical pathways mediating angiogenesis is critical to the identification of new molecular targets for therapeutic applications.
血管生成是一种正常的生物学过程,在此过程中,新的血管由已有的血管生长形成。通过靶向促血管生成因子(包括血管内皮生长因子(VEGF)、血管生成素-1(Ang-1)、碱性成纤维细胞生长因子(bFGF)、肝细胞生长因子和血小板衍生生长因子(PDGF))来阻止实体瘤中的血管生成,目前正在作为癌症治疗方法进行研究。同时靶向参与这些因子转录和翻译后调控的细胞信号通路可能会产生积极的治疗效果。其中一条这样的通路就是Wnt信号通路。Wnt最初是在感染小鼠乳腺肿瘤病毒的小鼠中发现的,对于增进我们对肿瘤发生和发育的理解至关重要。在这篇综述中,我们总结了Wnt信号通路对血管生成重要性的分子和细胞层面内容,包括β-连环蛋白依赖性促血管生成机制,以及对Wnt拮抗剂的研究,如已被证明可抑制血管生成的分泌型卷曲相关蛋白家族(SFRPs)。对介导血管生成的生化通路潜在复杂性的日益了解,对于确定治疗应用的新分子靶点至关重要。