COX-2 drives metastatic breast cells from brain lesions into the cerebrospinal fluid and systemic circulation
Menée à l'aide d'un modèle murin et sur neuf patientes atteintes d'un cancer du sein avec métastases cérébrales, cette étude met en évidence des mécanismes par lesquels la protéine COX-2 favorise la dissémination de cellules tumorales dans le sang périphérique et le liquide céphalo-rachidien
Breast cancer is among the most common malignancies that metastasize to the brain, with 15-20% of metastatic breast cancer patients eventually developing brain metastases. We previously reported a method to enumerate tumor cells in the cerebrospinal fluid (CSF) of breast cancer patients with central nervous system (CNS) metastases, a setting that lacks sufficiently informative biomarkers. Here we show that breast cancer cells can spontaneously disseminate into the CSF from brain lesions in mice in a COX-2-dependent manner and can escape from the CNS to systemic circulation. Enumeration of tumor cells in the peripheral blood (CTCs) and CSF (CSFTCs) of nine breast cancer patients with brain metastases revealed dynamic changes in tumor cell burden in both the peripheral blood and CSF compartments that correlated with clinical disease progression. Interestingly, four of the enrolled patients exhibited rapid intercompartmental transitioning of the disease reflected in the CTC and CSFTC counts that preceded corresponding evidence by clinical imaging or neurological symptoms. Two of these patients had systemic disease recurrence involving the primary malignant site. Intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence that may involve tumor self-seeding. Our findings demonstrate the involvement of COX-2 in the genesis of CSFTCs and suggest that COX-2 inhibitors should be investigated in breast cancer patients with brain metastases for their ability to reduce CSFTC counts and prevent systemic recurrence.