IMR Press / FBL / Volume 26 / Issue 9 / DOI: 10.52586/4969
Open Access Review
The role of astrocytes in brain metastasis at the interface of circulating tumour cells and the blood brain barrier
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1 School of Life Sciences, University of Sussex, BN1 9QG Falmer, Brighton, UK
2 College of Medicine and Health, University of Exeter, EX1 2LU Exeter, Devon, UK
3 Royal Devon and Exeter NHS Foundation Trust, EX2 7JU Exeter, Devon, UK
*Correspondence: (Georgios Giamas); (Md Zahidul Islam Pranjol)
Front. Biosci. (Landmark Ed) 2021, 26(9), 590–601;
Submitted: 22 June 2021 | Revised: 19 July 2021 | Accepted: 4 August 2021 | Published: 30 September 2021
(This article belongs to the Special Issue The dynamic roles of glial and stromal cells in neurological diseases)
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Tumour metastasis to the brain is a complex process involving crosstalk between the circulating tumour cells and the blood brain barrier (BBB). Astrocytes, which reside in the abluminal surface of the microvasculature of the BBB, are now known to play an essential role in tumour cell migration and invasion into the brain parenchyma. For instance, pro-inflammatory astrocyte secretions, including TNF-α, IL-6, CXCL10 as well as polyunsaturated fatty acids interact with circulating tumour cells to promote migration and proliferation. Additionally, astrocyte and tumour cell derived MMPs play a vital role in tumour cell invasion through the BBB. Understanding these complex interactions between tumour cells and astrocytes in the tumour microenvironment may contribute to the development of novel therapeutics for brain metastasis. Therefore, in this review, we present key interactions within the neurovascular unit of the BBB in the tumour microenvironment that significantly aids cancer metastasis, focusing particularly on astrocytes.

Blood brain barrier
Fig. 1.
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