Branco Helena, Xavier Cristina P R, Riganti Chiara, Vasconcelos M Helena
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal; Department of Biological Sciences, FFUP - Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal; Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal.
Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189244. doi: 10.1016/j.bbcan.2024.189244. Epub 2024 Dec 11.
In the past years, increasing attention has been paid to the role of extracellular vesicles (EVs) as mediators of intercellular communication in cancer. These small size particles mediate the intercellular transfer of important bioactive molecules involved in malignant initiation and progression. Hypoxia, or low partial pressure of oxygen, is recognized as a remarkable feature of solid tumors and has been demonstrated to exert a profound impact on tumor prognosis and therapeutic efficacy. Indeed, the high-pitched growth rate and chaotic neovascular architecture that embodies solid tumors results in a profound reduction in oxygen pressure within the tumor microenvironment (TME). In response to oxygen-deprived conditions, tumor cells and their surrounding milieu develop homeostatic adaptation mechanisms that contribute to the establishment of a pro-tumoral phenotype. Latest evidence suggests that the hypoxic microenvironment that surrounds the tumor bulk may be a clincher for the observed elevated levels of circulating EVs in cancer patients. Thus, it is proposed that EVs may play a role in mediating intercellular communication in response to hypoxic conditions. This review focuses on the EVs-mediated crosstalk that is established between tumor cells and their surrounding immune, endothelial, and stromal cell populations, within the hypoxic TME.
在过去几年中，细胞外囊泡（EVs）作为癌症中细胞间通讯介质的作用受到了越来越多的关注。这些小尺寸颗粒介导参与恶性肿瘤起始和进展的重要生物活性分子的细胞间转移。缺氧，即低氧分压，被认为是实体瘤的一个显著特征，并已被证明对肿瘤预后和治疗效果有深远影响。事实上，实体瘤的高生长速率和混乱的新生血管结构导致肿瘤微环境（TME）中的氧分压大幅降低。为了应对缺氧条件，肿瘤细胞及其周围环境会发展出稳态适应机制，这有助于建立促肿瘤表型。最新证据表明，肿瘤主体周围的缺氧微环境可能是癌症患者循环EVs水平升高的关键因素。因此，有人提出EVs可能在介导缺氧条件下的细胞间通讯中发挥作用。本综述重点关注在缺氧TME中肿瘤细胞与其周围免疫、内皮和基质细胞群体之间通过EVs建立的相互作用。
