癌症转移中血管通透性的调节,Cancer Science

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癌症转移中血管通透性的调节
Cancer Science ( IF 4.5 ) Pub Date : 2021-05-09 , DOI: 10.1111/cas.14942
Takeshi Tomita ₁ , Masayoshi Kato ₁ , Sachie Hiratsuka ₁

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血管通透性的增强对于癌症转移是必不可少的。内皮屏障功能减弱会增强血管通透性。在微血管系统中移动的循环肿瘤细胞倾向于在血管通透性增强的位置侵入基质组织。许多基础研究已经通过使用基因修饰的动物和细胞确定了渗透性因素。这些因素直接/间接地与内皮细胞相互作用。在这里，我们回顾血管通透性因素及其分子机制。在外渗过程中还讨论了肿瘤细胞和内皮细胞之间的相互作用，这是肿瘤转移中最关键的步骤之一。在某些情况下，原发性肿瘤可以通过分泌通透性因子来操纵远程器官的通透性。此外，糖萼的重要性，还描述了其覆盖内皮细胞表面，控制血管通透性和肿瘤转移。此外，还介绍了对小鼠模型研究中发现的高渗透区域的分析。它清楚地表明，由于远处原发肿瘤的影响，荷瘤小鼠肺具有高渗透性区域，并且在该区域观察到纤维蛋白原沉积。鉴于据报道纤维蛋白原是一种通透性因子和炎症的关键调节剂，消除纤维蛋白原沉积可能会预防未来的转移。它清楚地表明，由于远处原发肿瘤的影响，荷瘤小鼠肺具有高渗透性区域，并且在该区域观察到纤维蛋白原沉积。鉴于据报道纤维蛋白原是一种通透性因子和炎症的关键调节剂，消除纤维蛋白原沉积可能会预防未来的转移。它清楚地表明，由于远处原发肿瘤的影响，荷瘤小鼠肺具有高渗透性区域，并且在该区域观察到纤维蛋白原沉积。鉴于据报道纤维蛋白原是一种通透性因子和炎症的关键调节剂，消除纤维蛋白原沉积可能会预防未来的转移。

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Regulation of vascular permeability in cancer metastasis

Enhancement of vascular permeability is indispensable for cancer metastasis. Weakened endothelial barrier function enhances vascular permeability. Circulating tumor cells moving in the microvasculature tend to invade into stromal tissue at the location where vascular permeability is enhanced. Many basic studies have identified permeability factors by using gene-modified animals and cells. These factors directly/indirectly interact with endothelial cells. Here, we review vascular permeability factors and their molecular mechanisms. Interactions between tumor cells and endothelial cells are also discussed in the process of extravasation, one of the most critical steps in tumor metastasis. In some cases, primary tumors can manipulate permeability in a remote organ by secreting permeability factors. In addition, the importance of glycocalyx, which covers the endothelial cell surface, in controlling vascular permeability and tumor metastasis is also described. Furthermore, analysis of the hyperpermeable region found in a mouse model study is introduced. It clearly showed that tumor-bearing mouse lungs had a hyperpermeable region due to the influence of a remote primary tumor, and fibrinogen deposition was observed in that region. Given that fibrinogen was reported to be a permeability factor and a key regulator of inflammation, eliminating fibrinogen deposition may prevent future metastasis.

更新日期：2021-05-09

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