外泌体:精准肿瘤学的明星

Exosome:A rising star in the era of precision oncology

外泌体是指由细胞分泌具有生物活性的囊泡,它直径一般为30~150 nm,具有脂质双层膜.外泌体包含了分泌细胞的分子,如酯类、蛋白质和核酸等.外泌体在生命体内承担着传递生物分子以及帮助细胞之间信息交流的角色.本文介绍了外泌体的定义、组成以及受体细胞内吞外泌体的方式,探讨了外泌体在癌症液体活检以及在肿瘤发生、发展、转移和逃避免疫监视中的作用.系统地总结了外泌体作为肿瘤发生、发展以及恶性程度的生物标志物的研究进展,并进一步探讨了外泌体在肿瘤治疗中作为治疗靶点以及载体所起到的作用和意义.最后对外泌体在临床中的潜在应用进行了展望,为今后肿瘤诊断治疗提供新的思路.

Exosomes are dish-shaped phospholipid bilayer-enclosed membranous vesicles with diameter range of 30–150 nm. Exosomes as stable vesicles contain various bioactive molecules derived from the cells of parental origin, including proteins, lipids, DNA fragments, m RNAs, mi RNAs, lnc RNAs etc. Exosomes are secreted by almost all kinds of cells. Here, we focus on the application of exosomes in precision oncology. Nowadays, accumulating evidence suggests that cancer cells release the excessive amounts of exosomes compared to normal cells. The communications through exosomes between cancer cells and cancer/normal cells could make the exchange of genetic information and reprogramming of the recipient cells. Besides, the tumor-derived exosomes contribute the establishment of pre-metastatic niche and distant tissue site for metastasis of cancer cells. That may leads to cancer initiation, progression, metastasis of cancer cells and escaping from immune cell surveillance. In this review, we summarize the definition, composition and the potential diagnostic/therapeutic applications of exosomes. We introduce that there are several kinds of proteins enriched in exosomes such as TSG101, HSP70, CD9 and so on, which could be as the biomarkers to monitor the qualification and purification of exosomes we purified, in which play a pivotal role in exosome research. We describe the ways of recipient cells uptaking exosomes into themselves and the methods of exosome purification. Furthermore, we focus on non-invasive liquid biopsies in oncology, relying on analyzing material including molecules as well as whole cells that are found in bodily fluids such as blood and urine. Liquid biopsies are now in quick development and have been being an intriguing topic. We discuss the potential role of circulating tumor cells, circulating tumor-derived DNA/RNAs, and exosomes in liquid biopsy of cancer. We discriminate their characteristics and focus on exosomes that are used in liquid biopsy. Because the biomolecules in exosomes are derived from their parental cells, these contents are resembled between with each other. On this basis, it is conformed that they can reflect the dynamic information for genetic or signaling alteration of their cells of origin. We also highlighted its advanced progression in cancer diagnosis and therapeutic targets. It has been assumed that their contents such as nucleotides or proteins are abnormally enriched in tumor-derived ones compared to the normal, such as glypican-1 in pancreatic cancer and CD63 in the melanoma, which have the potential to be diagnostic biomarkers in cancers. The advanced studies have shown the difference between exosomes derived from tumor cells and normal cells, which may mediate different signaling pathways of the recipient cells. These facts indicate that we could transform exosomes to make it a medium to mediate agents to the recipient cells or a tool for treatment. For example, exosomes can serve as specific delivery vehicles loaded siR NAs/sh RNAs targeted to mR NAs, proteins or small molecules, as a tool of gene therapy. We also point out that we are still in early step of understanding the nature and extent of the involvement of exosomes in physiology and therapeutic targets. We highlight that these will shed light on the new strategy for cancer diagnosis and therapy. The advanced studies in exosomes we presented may make greater contribution to overcome a variety of cancer in the era of precision oncology.