Mortezaee Keywan, Majidpoor Jamal
Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.
Med Oncol. 2023 Mar 24;40(5):128. doi: 10.1007/s12032-023-01995-x.
Extracellular vesicles (EVs) are emerging as key mediators of cell-to-cell communications and signal transporters between tumor and stroma, and hypoxia is a critical characteristic of tumor microenvironment (TME) in solid cancers. Hypoxia stimulates tumor cells to generate and secrete more EVs, and the EVs shed from cancer transfer biological information to boost hypoxia and hypoxia inducible factor (HIF) functionality. Hypoxia alters EV secretome profile to carry pro-tumorigenic factors for promoting numerous tumor-related processes including increased cancer cell proliferation and survival, immune escape, aberrant angiogenesis, and invasion and metastasis. Exosomal hypoxia inducible factor (HIF)-1α is an essential driver of epithelial-mesenchymal transition (EMT) and stemness profile in cancer. Hypoxic cancer-derived EVs are also contributed to therapy resistance. In fact, EVs are messengers of hypoxic tolerance in cancer, which enable adaptation of tumor cells to changes occurring within TME for their further resistance and metastasis. Tracing EVs shed from hypoxic tumor cells into plasma provide important information about the genomic signature of cancer. In this review, we aimed to discuss about key tumorigenic events promoted by inter-connections between hypoxia and EVs, mainly exosomes, secreted into tumor area focusing on key hallmarks of cancer.
细胞外囊泡（EVs）正逐渐成为肿瘤与基质之间细胞间通讯和信号转运的关键介质，而缺氧是实体癌肿瘤微环境（TME）的一个关键特征。缺氧刺激肿瘤细胞产生并分泌更多的细胞外囊泡，癌症释放的细胞外囊泡传递生物信息以增强缺氧和缺氧诱导因子（HIF）的功能。缺氧改变细胞外囊泡分泌组图谱，使其携带促肿瘤因子，促进包括癌细胞增殖和存活增加、免疫逃逸、异常血管生成以及侵袭和转移在内的众多肿瘤相关过程。外泌体缺氧诱导因子（HIF）-1α是癌症上皮-间质转化（EMT）和干性特征的重要驱动因素。缺氧的癌症来源的细胞外囊泡也导致治疗耐药性。事实上，细胞外囊泡是癌症中缺氧耐受的信使，使肿瘤细胞能够适应TME内发生的变化，从而进一步产生耐药性和转移。追踪缺氧肿瘤细胞释放到血浆中的细胞外囊泡，可为癌症的基因组特征提供重要信息。在本综述中，我们旨在讨论缺氧与分泌到肿瘤区域的细胞外囊泡（主要是外泌体）之间的相互联系所促进的关键致癌事件，重点关注癌症的关键特征。
