Prognosis for metastatic spread to the central nervous system (CNS) is poor due to a lack of effective chemotherapeutic options. There is limited understanding of the biology underlying the progression of malignant tumors to a brain-metastatic phenotype, and a preclinical model of spontaneous CNS metastases would facilitate the study of such lesions. Cruz-Munoz and colleagues report for the first time an animal model of spontaneous CNS metastasis from human melanoma that recapitulates the metastatic cascade in which tumor spreads from a primary orthotopic site leading to the formation of metastatic lesions, primarily in the brain parenchyma as seen in the clinic. Cell lines generated from the metastatic lesions have an increased ability to proliferate in brain conditioned medium and display enhanced adhesion to lung and brain endothelial cells. This model will enable further studies to examine the sequence of alterations that occurs during the progression from primary melanoma toward spontaneous CNS metastasis. For details, see the article by Cruz-Munoz and colleagues on page 4500 of this issue.

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