Scarpellino Giorgia, Munaron Luca, Cantelmo Anna Rita, Fiorio Pla Alessandra
Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy.
Laboratoire de Cell Physiology, Université de Lille, Department of Life Sciences, Univ. Lille, Inserm, U1003 - PHYCEL, Lille, France.
Rev Physiol Biochem Pharmacol. 2022;182:111-137. doi: 10.1007/112_2020_32.
Calcium (Ca)-permeable channels are key players in different processes leading to blood vessel formation via sprouting angiogenesis, including endothelial cell (EC) proliferation and migration, as well as in controlling vascular features which are typical of the tumor vasculature.In this review we present an up-to-date and critical view on the role of Ca-permeable channels in tumor vascularization, emphasizing on the dual communication between growth factors (mainly VEGF) and Ca signals. Due to the complexity of the tumor microenvironment (TME) as a source of multiple stimuli acting on the endothelium, we aim to discuss the close interaction between chemical and physical challenges (hypoxia, oxidative stress, mechanical stress) and endothelial Ca-permeable channels, focusing on transient receptor potential (TRP), store-operated Ca channels (SOCs), and mechanosensitive Piezo channels. This approach will depict their crucial contribution in regulating key properties of tumor blood vessels, such as recruitment of endothelial progenitors cells (EPCs) in the early steps of tumor vascularization, abnormal EC migration and proliferation, and increased vascular permeability. Graphical abstract depicting the functional role of Ca-permeable TRP, SOCs and Piezo channels in the biological processes regulating tumor angiogenesis in presence of both chemical (oxidative stress and oxygen levels) and mechanical stimuli (ECM stiffness). SOCs store-operated Ca channels, TRPA transient receptor potential ankyrin, TRPV transient receptor potential vanilloid, TRPC transient receptor potential canonical, TRPM transient receptor potential melastatin, TRPM transient receptor potential vanilloid, O oxygen, ECM extracellular matrix.
钙（Ca）通透通道是通过芽生血管生成导致血管形成的不同过程中的关键参与者，包括内皮细胞（EC）的增殖和迁移，以及控制肿瘤血管系统特有的血管特征。在本综述中，我们对Ca通透通道在肿瘤血管生成中的作用提出了最新的批判性观点，强调生长因子（主要是血管内皮生长因子）与Ca信号之间的双重通讯。由于肿瘤微环境（TME）作为作用于内皮细胞的多种刺激源的复杂性，我们旨在讨论化学和物理刺激（缺氧、氧化应激、机械应激）与内皮Ca通透通道之间的密切相互作用，重点关注瞬时受体电位（TRP）、储存操纵性Ca通道（SOCs）和机械敏感性Piezo通道。这种方法将描述它们在调节肿瘤血管关键特性方面的关键作用，例如在肿瘤血管生成早期募集内皮祖细胞（EPCs）、异常的EC迁移和增殖以及增加的血管通透性。示意图描绘了在化学刺激（氧化应激和氧水平）和机械刺激（细胞外基质硬度）存在的情况下，Ca通透TRP、SOCs和Piezo通道在调节肿瘤血管生成生物学过程中的功能作用。SOCs储存操纵性Ca通道，TRPA瞬时受体电位锚蛋白，TRPV瞬时受体电位香草酸，TRPC瞬时受体电位典型，TRPM瞬时受体电位褪黑素，TRPM瞬时受体电位香草酸，O氧，ECM细胞外基质
