Reactive astrocytes promote the metastatic growth of breast cancer stem‐like cells by activating Notch signalling in brain

Autor: Fei Xing, Aya Kobayashi, Hiroshi Okuda, Misako Watabe, Sudha K. Pai, Puspa R. Pandey, Shigeru Hirota, Andrew Wilber, Yin‐Yuan Mo, Brian E. Moore, Wen Liu, Koji Fukuda, Megumi Iiizumi, Sambad Sharma, Yin Liu, Kerui Wu, Elizabeth Peralta, Kounosuke Watabe
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 5, Iss 3, Pp 384-396 (2013)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.1002/emmm.201201623
Popis: Abstract Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the brain highly expressed IL‐1β which then ‘activated’ surrounding astrocytes. This activation significantly augmented the expression of JAG1 in the astrocytes, and the direct interaction of the reactivated astrocytes and cancer stem‐like cells (CSCs) significantly stimulated Notch signalling in CSCs. We also found that the activated Notch signalling in CSCs up‐regulated HES5 followed by promoting self‐renewal of CSCs. Furthermore, we have shown that the blood‐brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis in vivo. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re‐establish their niche for their self‐renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease.
Databáze: Directory of Open Access Journals
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