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可视化癌症转移:从机制研究到药物开发。

Visualizing cancer extravasation: from mechanistic studies to drug development.

机构信息

Joint Department of Biomedical Engineering, North Carolina State University & University of North Carolina at Chapel Hill, Raleigh, NC, USA.

Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, 27607, USA.

出版信息

Cancer Metastasis Rev. 2021 Mar;40(1):71-88. doi: 10.1007/s10555-020-09942-2. Epub 2020 Nov 6.

Abstract

Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both in vitro and in vivo cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients.

摘要

转移是一个多步骤的过程,占大多数癌症相关死亡的原因。在转移扩散结束时,循环肿瘤细胞(CTC)需要在转移部位的血管外渗,以形成新的定植。尽管癌细胞外渗是癌症转移的关键步骤,但由于对调节这一过程的分子机制缺乏透彻的了解,目前的抗转移策略并没有成功地针对这一过程。本综述重点介绍了癌症外渗可视化技术的最新进展,包括体外和体内癌症外渗模型的发展,这些模型揭示了潜在的机制。具体来说,使用这些技术可以成功探测到多个癌症外渗阶段,如与内皮细胞的黏附和跨内皮迁移。此外,不同细胞黏附分子、趋化因子和生长因子以及这些阶段中的机械因素的作用也得到了很好的说明。对癌症外渗机制的更深入了解为我们提供了新的机会,以推进抗外渗药物和治疗方法的发现,并改善癌症患者的预后。

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