Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies
Teng Zhou, Yuxin Yan, Mingxi Lin, Cheng Zeng, Xinhui Mao, Yifei Zhu, Jinlu Han, Doudou Li, Jian Zhang
Abstract
BrMs represent a significant clinical challenge due to its high incidence, complex biology, and poor prognosis. Astrocytes, the predominant glial cells in the central nervous system, are increasingly recognized for their central role in shaping the brain microenvironment and driving the progression of brain metastases. This review highlights the multifaceted contributions of astrocytes to the metastatic cascade, including their involvement in tumor cell invasion, modulation of the blood-brain barrier, and establishment of a pro-metastatic niche. Astrocytes interact with tumor cells through various mechanisms, such as forming gap junctions, secreting factors that enhance tumor survival, and supporting immune evasion. These interactions promote tumor growth and protect metastatic cells from chemotherapy and radiotherapy, complicating current treatment strategies. Furthermore, astrocytes help reshape the brain microenvironment to support tumor adaptation and expansion, making them critical players in both the early and late stages of metastasis. Emerging therapeutic approaches are focused on disrupting astrocyte-tumor interactions, with strategies targeting astrocyte-driven communication pathways, immune modulation, and metabolic support systems. Nanotechnology and precision medicine also offer novel opportunities to improve drug delivery across BBB and directly target the astrocyte-tumor axis. This review underscores the importance of further research to fully understand the role of astrocytes in brain metastasis and develop therapies that leverage this knowledge to improve patient outcomes.