Breast-to-brain metastasis is exacerbated with chemotherapy through blood-cerebrospinal fluid barrier and induces Alzheimer's-like pathology.

ABSTRACT: Control of breast-to-brain metastasis remains an urgent unmet clinical need. While chemotherapies are essential in reducing systemic tumor burden, they have been shown to promote non-brain metastatic invasiveness and drug-driven neurocognitive deficits through the formation of neurofibrillary tangles (NFT), independently. Now, in this study, we investigated the effect of chemotherapy on brain metastatic progression and promoting tumor-mediated NFT. Results show chemotherapies increase brain-barrier permeability and facilitate enhanced tumor infiltration, particularly through the blood-cerebrospinal fluid barrier (BCSFB). This is attributed to increased expression of matrix metalloproteinase 9 (MMP9) which, in turn, mediates loss of Claudin-6 within the choroid plexus cells of the BCSFB. Im

SUBMITTER: Saatian B 

PROVIDER: S-EPMC10769085 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature