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癌症进展与抗癌治疗中细胞外囊泡的研究趋势

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy.

作者信息

Sinha Dona, Roy Sraddhya, Saha Priyanka, Chatterjee Nabanita, Bishayee Anupam

机构信息

Department of Receptor Biology and Tumour Metastasis, Chittaranjan National Cancer Institute, Kolkata 700 026, India.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.

出版信息

Cancers (Basel). 2021 Jan 17;13(2):326. doi: 10.3390/cancers13020326.

Abstract

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

摘要

外泌体是源自内体的双层细胞外纳米囊泡,在癌症生物学的许多方面都发挥着作用,已成为研究的主要焦点之一。源自各种细胞的外泌体携带与其起源细胞相似的物质,并且与其他细胞外囊泡相比,其产生方式有所不同。本综述试图涵盖外泌体生物发生的各个方面,包括货物、内体的Rab依赖性和Rab非依赖性分泌以及外泌体内化。肿瘤来源的外泌体的生物活性分子因其普遍存在且体积小,可迁移至远端部位并传播致癌信号和表观遗传调控,调节肿瘤微环境并促进免疫逃逸、肿瘤进展和导致癌症进展的耐药性。针对肿瘤来源外泌体的改进策略包括抑制外泌体摄取、调节外泌体货物和去除外泌体。除了促肿瘤作用外,外泌体货物已被选择性地用于诊断、免疫治疗、疫苗开发、RNA治疗、干细胞治疗、药物递送以及逆转癌症的化疗耐药性。然而,在成功将外泌体用于癌症诊断和治疗之前,必须面对几个挑战,包括对外泌体生物发生和蛋白质分选的深入了解、外泌体的完美和纯净分离、大规模生产、更好的装载效率以及外泌体的靶向递送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe3/7829710/da01cd3658e2/cancers-13-00326-g001.jpg

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