McGill University and Research Institute of the McGill University Health Centre, Canada.
McGill University and Research Institute of the McGill University Health Centre, Canada; Department of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Semin Cancer Biol. 2022 Dec;87:196-213. doi: 10.1016/j.semcancer.2022.11.003. Epub 2022 Nov 10.
Cancer progression impacts and exploits the vascular system in several highly consequential ways. Among different types of vascular cells, blood cells and mediators that are engaged in these processes, endothelial cells are at the centre of the underlying circuitry, as crucial constituents of angiogenesis, angiocrine stimulation, non-angiogenic vascular growth, interactions with the coagulation system and other responses. Tumour-vascular interactions involve soluble factors, extracellular matrix molecules, cell-cell contacts, as well as extracellular vesicles (EVs) carrying assemblies of molecular effectors. Oncogenic mutations and transforming changes in the cancer cell genome, epigenome and signalling circuitry exert important and often cancer-specific influences upon pathways of tumour-vascular interactions, including the biogenesis, content, and biological activity of EVs and responses of cancer cells to them. Notably, EVs may carry and transfer bioactive, oncogenic macromolecules (oncoproteins, RNA, DNA) between tumour and vascular cells and thereby elicit unique functional changes and forms of vascular growth and remodeling. Cancer EVs influence the state of the vasculature both locally and systemically, as exemplified by cancer-associated thrombosis. EV-mediated communication pathways represent attractive targets for therapies aiming at modulation of the tumour-vascular interface (beyond angiogenesis) and could also be exploited for diagnostic purposes in cancer.
癌症的进展以多种非常重要的方式影响和利用血管系统。在不同类型的血管细胞、参与这些过程的血细胞和介质中，内皮细胞是潜在电路的核心，因为它们是血管生成、血管生成刺激、非血管生成血管生长、与凝血系统相互作用和其他反应的重要组成部分。肿瘤-血管相互作用涉及可溶性因子、细胞外基质分子、细胞-细胞接触以及携带分子效应器组装的细胞外囊泡 (EVs)。致癌基因突变和癌症细胞基因组、表观基因组和信号转导电路中的转化改变，对肿瘤-血管相互作用的途径施加重要的、通常是癌症特异性的影响，包括 EV 的生物发生、内容和生物学活性，以及癌细胞对它们的反应。值得注意的是，EV 可以在肿瘤细胞和血管细胞之间携带和传递生物活性的致癌大分子（癌蛋白、RNA、DNA），从而引起独特的功能变化和血管生长和重塑形式。癌症 EV 不仅影响局部的血管状态，还影响全身的血管状态，例如癌症相关的血栓形成。EV 介导的通讯途径是针对肿瘤-血管界面（超越血管生成）进行调节的治疗的有吸引力的靶点，也可用于癌症的诊断目的。
