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细胞外囊泡作为癌症治疗的新兴靶点:从基础到临床的最新进展。

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside.

机构信息

Departments of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC, USA.

Departments of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC, USA.

出版信息

Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):538-563. doi: 10.1016/j.bbcan.2017.10.001. Epub 2017 Oct 18.

Abstract

Extracellular vesicles (EVs) have emerged as important players of cancer initiation and progression through cell-cell communication. They have been recognized as critical mediators of extracellular communications, which promote transformation, growth invasion, and drug-resistance of cancer cells. Interestingly, the secretion and uptake of EVs are regulated in a more controlled manner than previously anticipated. EVs are classified into three groups, (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on their sizes and origins, and novel technologies to isolate and distinguish these EVs are evolving. The biologically functional molecules harbored in these EVs, including nucleic acids, lipids, and proteins, have been shown to induce key signaling pathways in both tumor and tumor microenvironment (TME) cells for exacerbating tumor development. While tumor cell-derived EVs are capable of reprogramming stromal cells to generate a proper tumor cell niche, stromal-derived EVs profoundly affect the growth, resistance, and stem cell properties of tumor cells. This review summarizes and discusses these reciprocal communications through EVs in different types of cancers. Further understanding of the pathophysiological roles of different EVs in tumor progression is expected to lead to the discovery of novel biomarkers in liquid biopsy and development of tumor specific therapeutics. This review will also discuss the translational aspects of EVs and therapeutic opportunities of utilizing EVs in different cancer types.

摘要

细胞外囊泡 (EVs) 通过细胞间通讯成为癌症发生和进展的重要参与者。它们被认为是细胞外通讯的关键介质,促进癌细胞的转化、生长、侵袭和耐药性。有趣的是,EVs 的分泌和摄取比以前预期的更受控制。EVs 根据其大小和来源分为三组:(i) 外泌体,(ii) 微泡 (MVs),和 (iii) 凋亡小体 (ABs),并且正在开发新的技术来分离和区分这些 EVs。这些 EVs 中包含的生物功能分子,包括核酸、脂质和蛋白质,已被证明可在肿瘤和肿瘤微环境 (TME) 细胞中诱导关键信号通路,从而加剧肿瘤的发展。虽然肿瘤细胞衍生的 EVs 能够重新编程基质细胞以产生适当的肿瘤细胞龛,但基质衍生的 EVs 会深刻影响肿瘤细胞的生长、耐药性和干细胞特性。本文综述并讨论了不同类型癌症中通过 EVs 进行的这些相互交流。进一步了解不同 EVs 在肿瘤进展中的病理生理作用有望导致在液体活检中发现新型生物标志物,并开发针对肿瘤的特异性治疗方法。本文还将讨论 EVs 的转化方面以及在不同癌症类型中利用 EVs 的治疗机会。

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