肺癌是全球癌症相关死亡的最常见原因。造成高死亡率的原因有多种，包括转移至多个器官，特别是大脑。外泌体通过重构远程目标器官的微环境和促进前转移微环境的形成，在肿瘤的转移中起着关键作用。由于星形胶质细胞对于维持大脑微环境的稳态至关重要，因此探索肺癌细胞来源的外泌体对星形胶质细胞的影响，以进一步理解肺癌脑转移的机制是非常有意义的。在H1299细胞来源的外泌体和SVG P12细胞共培养24小时后，星形胶质细胞的存活率降低，凋亡率升高。上清液中的细胞因子水平，包括GROα / CXCL1、IFN-γ、IL-3、IL-5、IL-15、LIF、M-CSF、NGF、PDGF和VEGF得到显著增强，而IL-7分泌显著降低。同时，有关凋亡的蛋白质MAP2K1、TUBA1C、RELA和CASP6被上调。不同表达的蛋白质参与调节代谢途径。H1299的外泌体可以诱导星形胶质细胞凋亡，并促进它们分泌促进炎症微环境和免疫抑制微环境形成的细胞因子，并影响它们的代谢途径，从而促进肺癌脑转移中形成的前转移微环境形成。 ©2023 The Author(s)。

Lung cancer is the most common cause of cancer-related death globally. There are several reasons for this high mortality rate, including metastasis to multiple organs, especially the brain. Exosomes play a pivotal role in tumor metastasis by remodeling the microenvironment of remote target organs and promoting the pre-metastatic niche's formation. Since astrocytes are indispensable for maintaining the homeostasis of brain microenvironment, it's of great interest to explore the influence of lung cancer cell-derived exosomes on astrocytes to further understand the mechanism of lung cancer brain metastasis.Twenty four h after co-culture of H1299 cell-derived exosomes and SVG P12 cells, the viability of astrocytes decreased and the apoptosis increased. The levels of cytokines in the supernatant including GROα/CXCL1, IFN-γ, IL-3, IL-5, IL-15, LIF, M-CSF, NGF, PDGF, and VEGF were significantly enhanced, while IL-7 secretion was significantly reduced. Meanwhile, apoptosis-related proteins MAP2K1, TUBA1C, RELA, and CASP6 were up-regulated. And the differentially expressed proteins were involved in regulating metabolic pathways.Exosomes of H1299 could induce apoptosis of astrocytes as well as promote their secretion of cytokines that were conducive to the formation of the inflammatory microenvironment and immunosuppressive microenvironment, and affect their metabolic pathways, thus facilitating the formation of pre-metastatic niche in lung cancer brain metastases.© 2023. The Author(s).