ArticleNeuro-oncology advances
Brain metastasis patient-derived xenograft models to characterize the contribution of brain microenvironment to metastatic outgrowth.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Brain metastasis is the most ominous form of cancer relapse. There is urgent need to develop preclinical mouse models to study brain metastasis and new therapeutic strategies. Patient derived xenograft Methods: A collection of surgically resected brain metastasis tissues from cancer patients were used to generate PDX models. Ectopic and orthotopic brain metastasis PDX models were generated and characterized. The tumor growth was tracked in both PDX models when treated with PPARγ antagonist. Results: The growth rate of PDX tumors increased over passages in our ectopic PDX models and maintains in the orthotopic PDX models. Brain stromal cells were absent in the ectopic PDX tumors. Brain metastasis cancer cells sustained the PPARγ expression in both ectopic and orthotopic PDX tumors, at the similar level as the original brain metastasis tissues. However, PPARγ antagonist only decreased tumor growth in the brain without affecting subcutaneous tumors. Conclusions: Our results show that PDX models are successfully generated from clinical brain metastasis tissues and maintain the molecular characteristics in the brain metastasis cancer cells. Moreover, our study indicates the importance of the brain microenvironment to the therapeutic response in brain metastasis.
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