Systemic cancer progression culminating in metastatic disease is implicitly dependent on tumour cell interactions with the vascular system. Indeed, different facets of the micro- and macro-vasculature can be regarded as rate-limiting ‘vascular checkpoints’ in the process of cancer dissemination. The underlying complex communication networks drive tumour neovascularization, angiogenesis, immunoregulation, activation of the coagulation system, angiocrine interactions, and non-angiogenic vascular responses across multiple cancer types. Yet, each cancer may represent a unique vascular interaction scenario raising a prospect of targeted modulation of blood and lymphatic vessels for therapeutic purposes, beyond the traditional notion of tumour anti-angiogenesis. While the emphasis of studies aiming to understand this circuitry has traditionally been on soluble, or ‘mono-molecular’ mediators, the rise of the particulate secretome encompassing heterogeneous subpopulations of extracellular vesicles (EVs; including exosomes) and particles (EPs) brings another dimension into the tumour–vascular communication web during the process of metastasis. EVs and EPs are nanosized cellular fragments, the unique nature of which lies in their ability to encapsulate, protect and deliver to target cells a range of bioactive molecular entities (proteins, RNA, DNA) assembled in ways that enable them to exert a wide spectrum of biological activities. EVs and EPs penetrate through biological barriers and are capable of intracellular uptake. Their emerging vascular functions in metastatic or infiltrative cancers are exemplified by their roles in pre-metastatic niche formation, thrombosis, vasectasia or angiocrine regulation of cancer stem cells. Here, we survey some of the related evidence supporting the biological, diagnostic and interventional significance of EVs/EPs (EVPs) in disseminated neoplastic disease.
系统性癌症进展最终导致转移性疾病，其过程隐性地依赖于肿瘤细胞与血管系统的相互作用。事实上，微血管和大血管系统的不同方面可被视为癌症扩散过程中的限速性“血管检查点”。这一潜在的复杂通讯网络驱动着多种癌症类型中的肿瘤新生血管形成、血管生成、免疫调节、凝血系统激活、血管分泌相互作用以及非血管生成性血管反应。然而，每种癌症可能代表独特的血管相互作用情景，这为超越传统肿瘤抗血管生成概念、针对性地调控血液和淋巴管以实现治疗目的提供了前景。尽管传统上理解这一网络的研究重点一直放在可溶性或“单分子”介质上，但包含细胞外囊泡（EVs；包括外泌体）和颗粒（EPs）异质性亚群的颗粒性分泌组的兴起，为转移过程中的肿瘤-血管通讯网络带来了另一个维度。EVs和EPs是纳米级的细胞碎片，其独特性质在于它们能够封装、保护并向靶细胞递送一系列生物活性分子实体（蛋白质、RNA、DNA），这些分子以特定方式组装，使其能够发挥广泛的生物活性。EVs和EPs能够穿透生物屏障并实现细胞内摄取。它们在转移性或浸润性癌症中新兴的血管功能体现在它们在转移前生态位形成、血栓形成、血管扩张或癌症干细胞的血管分泌调节等方面的作用。在此，我们综述了一些相关证据，这些证据支持EVs/EPs（统称为EVPs）在播散性肿瘤疾病中的生物学、诊断和干预意义。
The Role of Extracellular Vesicles in the Control of Vascular Checkpoints for Cancer Metastasis
肿瘤(癌症)患者之家