Jafari Reza, Rahbarghazi Reza, Ahmadi Mahdi, Hassanpour Mehdi, Rezaie Jafar
Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Shafa St, Ershad Blvd, P.O. BoX: 1138, 57147, Urmia, Iran.
Department of Immunology and Genetics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
J Transl Med. 2020 Dec 10;18(1):474. doi: 10.1186/s12967-020-02662-9.
The solid tumor microenvironment possesses a hypoxic condition, which promotes aggressiveness and resistance to therapies. Hypoxic tumor cells undergo broadly metabolic and molecular adaptations and communicate with surrounding cells to provide conditions promising for their homeostasis and metastasis. Extracellular vesicles such as exosomes originating from the endosomal pathway carry different types of biomolecules such as nucleic acids, proteins, and lipids; participate in cell-to-cell communication. The exposure of cancer cells to hypoxic conditions, not only, increases exosomes biogenesis and secretion but also alters exosomes cargo. Under the hypoxic condition, different signaling pathways such as HIFs, Rab-GTPases, NF-κB, and tetraspanin are involved in the exosomes biogenesis. Hypoxic tumor cells release exosomes that induce tumorigenesis through promoting metastasis, angiogenesis, and modulating immune responses. Exosomes from hypoxic tumor cells hold great potential for clinical application and cancer diagnosis. Besides, targeting the biogenesis of these exosomes may be a therapeutic opportunity for reducing tumorigenesis. Exosomes can serve as a drug delivery system transferring therapeutic compounds to cancer cells. Understanding the detailed mechanisms involved in biogenesis and functions of exosomes under hypoxic conditions may help to develop effective therapies against cancer.
实体瘤微环境处于缺氧状态，这会促进肿瘤的侵袭性和对治疗的抗性。缺氧的肿瘤细胞会发生广泛的代谢和分子适应性变化，并与周围细胞进行通讯，以维持其稳态和转移创造条件。源自内体途径的细胞外囊泡（如外泌体）携带不同类型的生物分子，如核酸、蛋白质和脂质，参与细胞间通讯。癌细胞暴露于缺氧条件下，不仅会增加外泌体的生物发生和分泌，还会改变外泌体的货物成分。在缺氧条件下，不同的信号通路，如缺氧诱导因子（HIFs）、Rab-GTPases、核因子κB（NF-κB）和四跨膜蛋白，参与外泌体的生物发生。缺氧的肿瘤细胞释放的外泌体通过促进转移、血管生成和调节免疫反应来诱导肿瘤发生。缺氧肿瘤细胞来源的外泌体在临床应用和癌症诊断方面具有巨大潜力。此外，针对这些外泌体的生物发生进行靶向干预可能是减少肿瘤发生的一个治疗机会。外泌体可以作为一种药物递送系统，将治疗性化合物传递给癌细胞。了解缺氧条件下外泌体生物发生和功能的详细机制，可能有助于开发有效的抗癌疗法。
