Department of Biological and Medical Sciences Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
Department of Pediatrics and Microbiology & Molecular Immunology University of Southern California-Keck School of Medicine Norris Comprehensive Cancer Center Children's Center for Cancer and Blood Diseases, Children's Hospital, Los Angeles, CA, USA.
Proteomics. 2017 Dec;17(23-24). doi: 10.1002/pmic.201600375. Epub 2017 Oct 25.
Drug resistance remains a major barrier to the successful treatment of cancer. The mechanisms by which therapeutic resistance arises are multifactorial. Recent evidence has shown that extracellular vesicles (EVs) play a role in mediating drug resistance. EVs are small vesicles carrying a variety of macromolecular cargo released by cells into the extracellular space and can be taken up into recipient cells, resulting in transfer of cellular material. EVs can mediate drug resistance by several mechanisms. They can serve as a pathway for sequestration of cytotoxic drugs, reducing the effective concentration at target sites. They can act as decoys carrying membrane proteins and capturing monoclonal antibodies intended to target receptors at the cell surface. EVs from resistant tumor cells can deliver mRNA, miRNA, long noncoding RNA, and protein inducing resistance in sensitive cells. This provides a new model for how resistance that arises can then spread through a heterogeneous tumor. EVs also mediate cross-talk between cancer cells and stromal cells in the tumor microenvironment, leading to tumor progression and acquisition of therapeutic resistance. In this review, we will describe what is known about how EVs can induce drug resistance, and discuss the ways in which EVs could be used as therapeutic targets or diagnostic markers for managing cancer treatment. While further characterization of the vesiculome and the mechanisms of EV function are still required, EVs offer an exciting opportunity in the fight against cancer.
耐药性仍然是癌症成功治疗的主要障碍。治疗耐药性产生的机制是多因素的。最近的证据表明，细胞外囊泡（EVs）在介导耐药性方面发挥作用。EVs 是由细胞释放到细胞外空间的携带多种大分子货物的小囊泡，可以被受体细胞摄取，导致细胞物质的转移。EVs 可以通过几种机制介导耐药性。它们可以作为细胞毒性药物隔离的途径，降低靶部位的有效浓度。它们可以作为携带膜蛋白的诱饵，捕获旨在靶向细胞表面受体的单克隆抗体。耐药肿瘤细胞的 EVs 可以递送 mRNA、miRNA、长非编码 RNA 和蛋白质，从而在敏感细胞中诱导耐药性。这为耐药性如何在异质性肿瘤中传播提供了一个新的模型。EVs 还介导肿瘤微环境中癌细胞和基质细胞之间的串扰，导致肿瘤进展和获得治疗耐药性。在这篇综述中，我们将描述已知的 EVs 如何诱导耐药性的情况，并讨论如何将 EVs 用作治疗靶点或诊断标志物来管理癌症治疗。尽管仍然需要进一步表征囊泡组和 EV 功能的机制，但 EVs 在对抗癌症方面提供了一个令人兴奋的机会。
