Development and characterization of a clinically relevant model of breast cancer brain metastasis

Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterization of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to lung, bone and brain but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumors. The 4T1Br4 model will provide a clinically relevant tool to evaluate novel therapies against brain metastasis. Tumor cells were FACS isolated from biological replicate primary tumors, including 3 x 'BrMet' brain-metastatic tumors, 11 x 'HighMet' highly metastatic tumors and 3 x 'NonMet' non-metastatic tumors for gene level expression profiling on Affymetrix GeneChip Mouse Exon 1.0 ST Arrays