AbstractSecreted class 3 semaphorins (Sema3), which signal through plexin receptors and mostly use neuropilins (Nrps) as co-receptors, were initially identified for their ability to steer navigating axons in the developing embryo. They were later found to control angiogenesis in physiological and pathological settings as well (Serini et al, 2013). Indeed, the development of a novel and aberrant vasculature is central to the pathogenesis of several human diseases, including cancer and vascular retinopathies (Goel et al, 2011). A large body of evidence demonstrates that in cancer, a massive regression of angiogenesis may trigger hypoxia-driven genetic programs, which in turn can overcome drug inhibitory mechanisms and ultimately favour cancer cell invasion and dissemination. Thus, an emerging concept in molecular medicine is to devise therapeutic strategies that, rather than simply inhibiting angiogenesis, can foster the re-establishment of a structural and functional normal network, a phenomenon often referred to as “vessel normalization” (Goel et al, 2011) (Fig 1). Of note, and in this context, Sema3A (Maione et al, 2009) and Sema3F (Wong et al, 2012) have been reported to favour the normalization of cancer vasculature and impair metastatic dissemination.
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机译：摘要最初鉴定出了3类信号量（Sema3），其通过plexin受体发出信号并主要使用神经纤毛蛋白（Nrps）作为共受体，从而具有引导发育中的胚轴突的能力。后来发现它们也能在生理和病理环境中控制血管生成（Serini et al，2013）。确实，新的异常脉管系统的发展对于包括癌症和血管视网膜病变在内的几种人类疾病的发病机理至关重要（Goel等人，2011）。大量证据表明，在癌症中，血管生成的大量消退可能触发缺氧驱动的基因程序，从而可以克服药物抑制机制并最终有利于癌细胞的侵袭和扩散。因此，分子医学中的一个新兴概念是设计治疗策略，而不是简单地抑制血管新生，而是可以促进结构和功能正常网络的重建，这种现象通常被称为“血管正常化”（Goel等， 2011）（图1）。值得注意的是，在这种情况下，据报道Sema3A（Maione等人，2009）和Sema3F（Wong等人，2012）有利于癌症脉管系统的正常化并损害转移性传播。
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