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

Fei Xing1,2, Aya Kobayashi1, Hiroshi Okuda1, Misako Watabe1, Sudha K. Pai1, Puspa R. Pandey1, Shigeru Hirota3, Andrew Wilber1, Yin-Yuan Mo1,2, Brian E. Moore4, Wen Liu1, Koji Fukuda1, Megumi Iiizumi1, Sambad Sharma2, Yin Liu2, Kerui Wu2, Elizabeth Peralta5, Kounosuke Watabe1,2*
Source: EMBO Mol Med
Publication Date: (2013)
Issue: 5(3): 384-96
Research Area:
Basic Research
Cells used in publication:
Astrocyte (NHA), human
Species: human
Tissue Origin: brain
Culture Media:


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-1ß 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