Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Nat Rev Clin Oncol. 2018 Oct;15(10):617-638. doi: 10.1038/s41571-018-0036-9.
The sustained growth, invasion, and metastasis of cancer cells depend upon bidirectional cell-cell communication within complex tissue environments. Such communication predominantly involves the secretion of soluble factors by cancer cells and/or stromal cells within the tumour microenvironment (TME), although these cell types have also been shown to export membrane-encapsulated particles containing regulatory molecules that contribute to cell-cell communication. These particles are known as extracellular vesicles (EVs) and include species of exosomes and shed microvesicles. EVs carry molecules such as oncoproteins and oncopeptides, RNA species (for example, microRNAs, mRNAs, and long non-coding RNAs), lipids, and DNA fragments from donor to recipient cells, initiating profound phenotypic changes in the TME. Emerging evidence suggests that EVs have crucial roles in cancer development, including pre-metastatic niche formation and metastasis. Cancer cells are now recognized to secrete more EVs than their nonmalignant counterparts, and these particles can be isolated from bodily fluids. Thus, EVs have strong potential as blood-based or urine-based biomarkers for the diagnosis, prognostication, and surveillance of cancer. In this Review, we discuss the biophysical properties and physiological functions of EVs, particularly their pro-metastatic effects, and highlight the utility of EVs for the development of cancer diagnostics and therapeutics.
癌细胞的持续生长、侵袭和转移依赖于复杂组织环境中细胞间的双向通讯。这种通讯主要涉及癌细胞和/或肿瘤微环境(TME)中的基质细胞分泌可溶性因子,尽管这些细胞类型也被证明可以输出含有调节分子的膜包裹颗粒,这些调节分子有助于细胞间通讯。这些颗粒被称为细胞外囊泡(EVs),包括外泌体和脱落的微囊泡等种类。EVs 携带的分子包括癌蛋白和癌肽、RNA 种类(例如 microRNAs、mRNAs 和长非编码 RNA)、脂质和 DNA 片段,从供体细胞传递到受体细胞,引发 TME 中深刻的表型变化。新出现的证据表明,EVs 在癌症发展中具有关键作用,包括前转移龛形成和转移。癌细胞现在被认为比非恶性细胞分泌更多的 EVs,并且可以从体液中分离出这些颗粒。因此,EVs 具有作为基于血液或尿液的癌症诊断、预后和监测的生物标志物的强大潜力。在这篇综述中,我们讨论了 EVs 的生物物理特性和生理功能,特别是它们的促转移作用,并强调了 EVs 在癌症诊断和治疗开发中的应用。