Abstract:
:The brain is a major site of relapse for several cancers, yet deciphering the mechanisms of brain metastasis remains a challenge because of the complexity of the brain tumor microenvironment (TME). To define the molecular landscape of brain metastasis from intact tissue in vivo, we employ an RNA-sequencing-based approach, which leverages the transcriptome of xenografts and distinguishes tumor cell and stromal gene expression with improved sensitivity and accuracy. Our data reveal shifts in epithelial and neuronal-like lineage programs in malignant cells as they adapt to the brain TME and the reciprocal neuroinflammatory response of the stroma. We identify several transcriptional hallmarks of metastasis that are specific to particular regions of the brain, induced across multiple tumor types, and confirmed in syngeneic models and patient biopsies. These data may serve as a resource for exploring mechanisms of TME co-adaptation within, as well as across, different subtypes of brain metastasis.
journal_name
Cell Repjournal_title
Cell reportsauthors
Wingrove E,Liu ZZ,Patel KD,Arnal-Estapé A,Cai WL,Melnick MA,Politi K,Monteiro C,Zhu L,Valiente M,Kluger HM,Chiang VL,Nguyen DXdoi
10.1016/j.celrep.2019.03.085subject
Has Abstractpub_date
2019-04-23 00:00:00pages
1277-1292.e7issue
4issn
2211-1247pii
S2211-1247(19)30424-3journal_volume
27pub_type
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