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Exosomes in hypoxia-induced remodeling of the tumor microenvironment.
Cancer Letters ( IF 9.7 ) Pub Date : 2020-05-27 , DOI: 10.1016/j.canlet.2020.05.018
Ashish Kumar 1 , Gagan Deep 2
Affiliation  

Exosomes are structurally and functionally pleiotropic nano-sized (~30–150 nm in diameter) extracellular vesicles (EVs) with endosomal origin. These vesicles are secreted by almost all cells and play a significant role in intercellular communication and bio-waste disposal. To a great extent, exosomes represent biological “snapshot” of parent cells, and their cargos (protein, nucleotides, lipids, and metabolites) are loaded uniquely under different pathophysiological conditions. For example, most cancerous cells secrete a higher amount of exosomes loaded with distinct cargos under stressful low oxygen condition i.e. hypoxia, a key characteristic of solid tumors responsible for disease aggressiveness and poor survival. Exosomes secreted under hypoxia (ExoHypoxic) play a vital role in aiding cancer cells crosstalk with its microenvironment constituents to create conditions advantageous for cancer growth and metastatic spread. In this review article, we have highlighted the effects of ExoHypoxic on various tumor microenvironment components involved in angiogenesis, survival, proliferation, pre-metastatic niches preparation, immunomodulation, epithelial-to-mesenchymal transition, invasion, metastasis, and drug resistance. We have also described key ExoHypoxic cargos (miRNA, proteins, etc) and their targets in the receipt cells, responsible for various biological effects. Finally, we have emphasized the applicability of ExoHypoxic as a biomarker of tumor hypoxia and disease prognosis.



中文翻译:

外泌体在低氧诱导的肿瘤微环境重塑中。

外泌体是具有内吞起源的多效性纳米大小(直径约30-150 nm)的细胞外囊泡(EV)。这些囊泡几乎由所有细胞分泌,并在细胞间通讯和生物废物处理中起重要作用。外泌体在很大程度上代表了亲代细胞的生物学“快照”,并且它们的货物(蛋白质,核苷酸,脂质和代谢产物)在不同的病理生理条件下被独特地装载。例如,大多数癌细胞在压力低的氧气条件下(即缺氧)分泌大量的外来体,这些外来体载有不同的货物,这是导致疾病侵袭性和不良生存的实体瘤的关键特征。缺氧下分泌的外泌体(低氧)在协助癌细胞与其微环境成分串扰以创造有利于癌症生长和转移扩散的条件方面发挥着至关重要的作用。在这篇综述文章中,我们强调了Exo低氧对涉及血管生成,存活,增殖,转移前小生境制备,免疫调节,上皮到间充质转化,侵袭,转移和耐药性的各种肿瘤微环境成分的影响。我们还描述了关键的Exo低氧货物(miRNA,蛋白质等)及其在接收细胞中的靶标,这些靶标负责各种生物学效应。最后,我们强调了Exo低氧作为肿瘤缺氧和疾病预后的生物标志物的适用性。

更新日期:2020-05-27
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