Astrocyte involvement in brain metastasis: from biological mechanisms to therapeutic strategies

被引：0
作者：
Zhou, Teng [1 ,2 ]
Yan, Yuxin [1 ,2 ]
Lin, Mingxi [1 ,2 ]
Zeng, Cheng [1 ,2 ]
Mao, Xinhui [3 ,4 ]
Zhu, Yifei [1 ,2 ]
Han, Jinlu [5 ]
Li, Dou-Dou [6 ]
Zhang, Jian [1 ,2 ]
机构：
[1] Fudan Univ, Dept Med Oncol, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China
[3] Fudan Univ, Eye & ENT Hosp, ENT Inst, Shanghai 200031, Peoples R China
[4] Fudan Univ, Eye & ENT Hosp, Dept Otorhinolaryngol, Shanghai 200031, Peoples R China
[5] Shanghai Jiao Tong Univ, Tongren Hosp, Dept Gastroenterol, Sch Med, Shanghai 200336, Peoples R China
[6] Shanghai Univ Med & Hlth Sci, Sch Clin Med, Shanghai, Peoples R China
来源：
CANCER AND METASTASIS REVIEWS | 2025年 / 44卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Astrocytes; Brain metastasis; Tumor microenvironment; BBB; Therapeutic targeting; BREAST-CANCER; TUMOR ANGIOGENESIS; MELANOMA-CELLS; GAP-JUNCTIONS; PROMOTE; MICROENVIRONMENT; ACTIVATION; SURVIVAL; PROLIFERATION; SPECIFICITY;
D O I：
10.1007/s10555-025-10276-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：18
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共 105 条
[1]   Brain metastases [J].
Achrol, Achal Singh ;
Rennert, Robert C. ;
Anders, Carey ;
Soffietti, Riccardo ;
Ahluwalia, Manmeet S. ;
Nayak, Lakshmi ;
Peters, Solange ;
Arvold, Nils D. ;
Harsh, Griffith R. ;
Steeg, Patricia S. ;
Chang, Steven D. .
NATURE REVIEWS DISEASE PRIMERS, 2019, 5 (1)
[2]   Physical activity and exercise health benefits: cancer prevention, interception, and survival [J].
Albini, Adriana ;
La Vecchia, Carlo ;
Magnoni, Francesca ;
Garrone, Ornella ;
Morelli, Danilo ;
Janssens, Jaak Ph. ;
Maskens, Alain ;
Rennert, Gad ;
Galimberti, Viviana ;
Corso, Giovanni .
EUROPEAN JOURNAL OF CANCER PREVENTION, 2025, 34 (01) :24-39
[3]   Heterogeneity of reactive astrocytes [J].
Anderson, Mark A. ;
Ao, Yan ;
Sofroniew, Michael V. .
NEUROSCIENCE LETTERS, 2014, 565 :23-29
[4]   Brain Energy Metabolism: Focus on Astrocyte-Neuron Metabolic Cooperation [J].
Belanger, Mireille ;
Allaman, Igor ;
Magistretti, Pierre J. .
CELL METABOLISM, 2011, 14 (06) :724-738
[5]   Matrix stiffening promotes a tumor vasculature phenotype [J].
Bordeleau, Francois ;
Mason, Brooke N. ;
Lollis, Emmanuel Macklin ;
Mazzola, Michael ;
Zanotelli, Matthew R. ;
Somasegar, Sahana ;
Califano, Joseph P. ;
Montague, Christine ;
LaValley, Danielle J. ;
John Huynh ;
Mencia-Trinchant, Nuria ;
Abril, Yashira L. Negron ;
Hassane, Duane C. ;
Bonassar, Lawrence J. ;
Butcher, Jonathan T. ;
Weiss, Robert S. ;
Reinhart-King, Cynthia A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (03) :492-497
[6]   Genes that mediate breast cancer metastasis to the brain [J].
Bos, Paula D. ;
Zhang, Xiang H. -F. ;
Nadal, Cristina ;
Shu, Weiping ;
Gomis, Roger R. ;
Nguyen, Don X. ;
Minn, Andy J. ;
van de Vijver, Marc J. ;
Gerald, William L. ;
Foekens, John A. ;
Massague, Joan .
NATURE, 2009, 459 (7249) :1005-U137
[7]   Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies [J].
Bowman, Robert L. ;
Klemm, Florian ;
Akkari, Leila ;
Pyonteck, Stephanie M. ;
Sevenich, Lisa ;
Quail, Daniela F. ;
Dhara, Surajit ;
Simpson, Kenishana ;
Gardner, Eric E. ;
Iacobuzio-Donahue, Christine A. ;
Brennan, Cameron W. ;
Tabar, Viviane ;
Gutin, Philip H. ;
Joyce, Johanna A. .
CELL REPORTS, 2016, 17 (09) :2445-2459
[8]   Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards [J].
Bronte, Vincenzo ;
Brandau, Sven ;
Chen, Shu-Hsia ;
Colombo, Mario P. ;
Frey, Alan B. ;
Greten, Tim F. ;
Mandruzzato, Susanna ;
Murray, Peter J. ;
Ochoa, Augusto ;
Ostrand-Rosenberg, Suzanne ;
Rodriguez, Paulo C. ;
Sica, Antonio ;
Umansky, Viktor ;
Vonderheide, Robert H. ;
Gabrilovich, Dmitry I. .
NATURE COMMUNICATIONS, 2016, 7
[9]   Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study [J].
Cagney, Daniel N. ;
Martin, Allison M. ;
Catalano, Paul J. ;
Redig, Amanda J. ;
Lin, Nancy U. ;
Lee, Eudocia Q. ;
Wen, Patrick Y. ;
Dunn, Ian F. ;
Bi, Wenya Linda ;
Weiss, Stephanie E. ;
Haas-Kogan, Daphne A. ;
Alexander, Brian M. ;
Aizer, Ayal A. .
NEURO-ONCOLOGY, 2017, 19 (11) :1511-1521
[10]  
Chen JF., 2025, Science Advances, V11, peads6021
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