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CXCR4 expression is associated with proneural-to-mesenchymal transition in glioblastoma.
Khan, A Basit; Lee, Sungho; Harmanci, Akdes Serin; Patel, Rajan; Latha, Khatri; Yang, Yuhui; Marisetty, Anantha; Lee, Hyun-Kyoung; Heimberger, Amy B; Fuller, Gregory N; Deneen, Benjamin; Rao, Ganesh.
Afiliación
  • Khan AB; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Lee S; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Harmanci AS; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Patel R; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Latha K; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Yang Y; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Marisetty A; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Lee HK; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • Heimberger AB; Department of Neurosurgery, Northwestern University, Chicago, Illinois, USA.
  • Fuller GN; Department of Pathology, MD Anderson Cancer Center, Houston, Texas, USA.
  • Deneen B; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
  • Rao G; Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
Int J Cancer ; 152(4): 713-724, 2023 02 15.
Article en En | MEDLINE | ID: mdl-36250346
Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial-mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high-grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single-cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell-autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Glioma Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Glioma Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos