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Background: Mechanism of brain metastasis of breast cancer is poorly understood.

Results: Inflammatory factors secreted from cancer cells degrade tight junction of BBB and stimulate the tumor-microenvironment cross-talk.

Conclusion: COX2-prostaglandins-MMP1 pathway promotes brain metastasis by tampering with BBB and up-regulating CCL7 in astrocytes for the growth of tumor initiating cells.

Significance: The COX2-prostaglandins-MMP1 pathway may serve as a novel therapeutic target for brain metastasis.

Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We …