Astrocyte plasticity shapes brain metastasis progression through tumor-astrocyte crosstalk

Rupleen Kaur; Nalin Gupta; Andrew Dhawan

doi:10.47248/chp2502010002

Cancer Heterogeneity and Plasticity 2025;2(1):0002 | https://doi.org/10.47248/chp2502010002

Review Open Access

Astrocyte plasticity shapes brain metastasis progression through tumor-astrocyte crosstalk

Rupleen Kaur ^1,2 , Nalin Gupta ³ , Andrew Dhawan ^2,4

1. School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
2. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44196, USA
3. Biomedical Engineering, Washington University in St. Louis, MO 63130, USA
4. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA

Correspondence: Andrew Dhawan

Academic Editor(s): Toru Kondo

Received: Oct 30, 2024 | Accepted: Dec 13, 2024 | Published: Jan 13, 2025

Cite this article: Kaur R, Gupta N, Dhawan A. Astrocyte plasticity shapes brain metastasis progression through tumor-astrocyte crosstalk. Cancer Heterog Plast 2025; 2(1):0002. https://doi.org/10.47248/chp2502010002

Abstract

Brain metastases are ten times more common than primary brain tumors and pose a significant clinical challenge. How brain metastatic tumor cells adapt to the unique and hostile brain microenvironment remains unclear. Astrocytes, the most abundant glial cells in the brain, are emerging as key mediators regulating the development of brain metastases. Initially anti-metastatic, astrocytes are reprogrammed by tumor-derived signals, transitioning into a pro-metastatic phenotype. Here, we review the roles of astrocytes in brain metastasis and describe the evidence for their phenotypic plasticity, the basis of astrocyte-tumor interactions, and potential therapeutic strategies targeting these processes.

Keywords

reprogrammed astrocytes, brain metastases, reactive astrocytes, tumor-associated astrocytes

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