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血管生成在炎症和癌症中的作用。

Contribution of Angiogenesis to Inflammation and Cancer.

作者信息

Aguilar-Cazares Dolores, Chavez-Dominguez Rodolfo, Carlos-Reyes Angeles, Lopez-Camarillo César, Hernadez de la Cruz Olga N, Lopez-Gonzalez Jose S

机构信息

Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City, Mexico.

Posgrado en Ciencias Biologicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.

出版信息

Front Oncol. 2019 Dec 12;9:1399. doi: 10.3389/fonc.2019.01399. eCollection 2019.

Abstract

During carcinogenesis, advanced tumors are surrounded by both stromal and immune cells, which support tumor development. In addition, inflammation and angiogenesis are processes that play important roles in the development of cancer, from the initiation of carcinogenesis, tumor and advanced stages of cancer. During acute inflammation, vascular hyperpermeability allows inflammatory mediators and immune response cells, including leukocytes and monocytes/macrophages, to infiltrate the site of damage. As a factor that regulates vascular permeability, vascular endothelial growth factor (VEGF) also plays a vital role as a multifunctional molecule and growth factor. Furthermore, stromal and immune cells secrete soluble factors that activate endothelial cells and favor their transmigration to eliminate the aggressive agent. In this review, we present a comprehensive view of both the relationship between chronic inflammation and angiogenesis during carcinogenesis and the participation of endothelial cells in the inflammatory process. In addition, the regulatory mechanisms that contribute to the endothelium returning to its basal permeability state after acute inflammation are discussed. Moreover, the manner in which immune cells participate in pathological angiogenesis release pro-angiogenic factors that contribute to early tumor vascularization, even before the angiogenic switch occurs, is also examined. Also, we discuss the role of hypoxia as a mechanism that drives the acquisition of tumor hallmarks that make certain cancers more aggressive. Finally, some combinations of therapies that inhibit the angiogenesis process and that may be a successful strategy for cancer patients are indicated.

摘要

在致癌过程中,晚期肿瘤被支持肿瘤发展的基质细胞和免疫细胞所包围。此外,炎症和血管生成是在癌症发展过程中发挥重要作用的过程,从致癌作用的起始、肿瘤形成到癌症晚期。在急性炎症期间,血管通透性增加使炎症介质和免疫反应细胞,包括白细胞和单核细胞/巨噬细胞,能够浸润损伤部位。作为调节血管通透性的一个因素,血管内皮生长因子(VEGF)作为一种多功能分子和生长因子也起着至关重要的作用。此外,基质细胞和免疫细胞分泌可溶性因子,激活内皮细胞并促进其迁移以清除侵袭因子。在这篇综述中,我们全面阐述了致癌过程中慢性炎症与血管生成之间的关系以及内皮细胞在炎症过程中的参与情况。此外,还讨论了急性炎症后内皮细胞恢复到基础通透性状态的调节机制。此外,还研究了免疫细胞参与病理性血管生成释放促血管生成因子的方式,这些因子在血管生成开关发生之前就有助于早期肿瘤血管形成。同时,我们讨论了缺氧作为一种驱动肿瘤获得某些使癌症更具侵袭性的特征的机制所起的作用。最后,指出了一些抑制血管生成过程的联合治疗方法,这些方法可能是癌症患者的成功治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d611/6920210/99217e17ba05/fonc-09-01399-g0001.jpg

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