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肿瘤衍生的外泌体的信号传递影响黑色素瘤的进展。

Signaling of Tumor-Derived sEV Impacts Melanoma Progression.

机构信息

Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland.

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.

出版信息

Int J Mol Sci. 2020 Jul 17;21(14):5066. doi: 10.3390/ijms21145066.

Abstract

Small extracellular vesicles (sEV or exosomes) are nanovesicles (30-150 nm) released both in vivo and in vitro by most cell types. Tumor cells produce sEV called TEX and disperse them throughout all body fluids. TEX contain a cargo of proteins, lipids, and RNA that is similar but not identical to that of the "parent" producer cell (i.e., the cargo of exosomes released by melanoma cells is similar but not identical to exosomes released by melanocytes), possibly due to selective endosomal packaging. TEX and their role in cancer biology have been intensively investigated largely due to the possibility that TEX might serve as key component of a "liquid tumor biopsy." TEX are also involved in the crosstalk between cancer and immune cells and play a key role in the suppression of anti-tumor immune responses, thus contributing to the tumor progression. Most of the available information about the TEX molecular composition and functions has been gained using sEV isolated from supernatants of cancer cell lines. However, newer data linking plasma levels of TEX with cancer progression have focused attention on TEX in the patients' peripheral circulation as potential biomarkers of cancer diagnosis, development, activity, and response to therapy. Here, we consider the molecular cargo and functions of TEX as potential biomarkers of one of the most fatal malignancies-melanoma. Studies of TEX in plasma of patients with melanoma offer the possibility of an in-depth understanding of the melanoma biology and response to immune therapies. This review features melanoma cell-derived exosomes (MTEX) with special emphasis on exosome-mediated signaling between melanoma cells and the host immune system.

摘要

小细胞外囊泡 (sEV 或外泌体) 是由大多数细胞类型在体内和体外释放的纳米囊泡 (30-150nm)。肿瘤细胞产生的 sEV 称为 TEX,并将其散布到所有体液中。TEX 包含与“亲本”产生细胞相似但不完全相同的蛋白质、脂质和 RNA 货物(即黑素瘤细胞释放的外泌体的货物与黑素细胞释放的外泌体相似但不完全相同),这可能是由于选择性内体包装。TEX 及其在癌症生物学中的作用已得到广泛研究,主要是因为 TEX 可能作为“液体肿瘤活检”的关键组成部分。TEX 还参与了癌症和免疫细胞之间的串扰,并在抑制抗肿瘤免疫反应中发挥关键作用,从而促进肿瘤进展。关于 TEX 分子组成和功能的大部分可用信息是使用从癌细胞系上清液中分离的 sEV 获得的。然而,将 TEX 的血浆水平与癌症进展相关联的最新数据引起了人们对患者外周循环中 TEX 的关注,因为 TEX 是癌症诊断、发展、活性和对治疗反应的潜在生物标志物。在这里,我们考虑 TEX 的分子货物和功能作为最致命的恶性肿瘤之一——黑色素瘤的潜在生物标志物。对黑色素瘤患者血浆中 TEX 的研究为深入了解黑色素瘤生物学和对免疫治疗的反应提供了可能。这篇综述以黑色素瘤细胞衍生的外泌体 (MTEX) 为特色,特别强调了黑色素瘤细胞与宿主免疫系统之间的外泌体介导的信号转导。

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