Hypoxia is a key feature of solid tumors, associated with disease aggressiveness and poor outcome. Besides undergoing broad intracellular molecular and metabolic adaptations, hypoxic tumor cells extensively communicate with their microenvironment to concoct conditions favorable for their survival, growth and metastatic spread. This mode of communication is through diverse secretory factors including exosomes (extracellular vesicles of endosomal origin and ∼30-150nm in diameter) which could carry package of molecular information including proteins, nucleic acids, lipids, and metabolites wrapped in lipid bilayer. Numerous studies have concluded that hypoxia promotes exosomes secretion by cancer cells. Moreover, exosomal cargo is considerably altered under hypoxia, dictating tumor cells communication with its local and distant microenvironment. In this review, we have summarized the effects of hypoxia on exosomes (Exo^Hypoxic) secretion and cargo sorting (miRNAs, proteins, lipids and metabolites) as well as their biological effects in local and distant microenvironment. We have described the key molecular mechanisms (e.g. HIF-1α, ceramides, RAB GTPases, tetraspanins, oxidative stress etc) involved in the production of Exo^Hypoxic. Lastly, we have highlighted the potential usefulness of Exo^Hypoxic in cancer prognosis as well as therapeutic opportunities in targeting Exo^Hypoxic.

缺氧是实体瘤的关键特征，与疾病侵袭性和不良预后有关。低氧肿瘤细胞除了经历广泛的细胞内分子和代谢适应性反应外，还与微环境进行广泛交流，以形成有利于其生存，生长和转移扩散的条件。这种交流方式是通过多种分泌因子实现的，包括外泌体（内体起源的细胞外囊泡，直径约30-150nm），可以携带分子信息，包括包裹在脂质双层中的蛋白质，核酸，脂质和代谢产物。大量研究得出结论，低氧促进癌细胞分泌外泌体。此外，在低氧条件下，外泌体的货物发生了很大变化，决定了肿瘤细胞与其局部和远处的微环境之间的通讯。^低氧分泌和货物分选（miRNA，蛋白质，脂质和代谢物）及其在局部和远距离微环境中的生物学作用。我们已经描述了涉及Exo^低氧生产的关键分子机制（例如HIF-1α，神经酰胺，RAB GTPases，四跨膜蛋白，氧化应激等）。最后，我们强调了Exo ^Hypoxic在癌症预后中的潜在作用以及靶向Exo ^Hypoxic的治疗机会。