Related Experiment Video
Updated: Sep 17, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Brain CD73 modulates interferon signaling to regulate glioblastoma invasion
Konstantina Kyritsi1, Jishi Ye1, Eugene Douglass2
1Department of Pathology, Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA.
Background:
Glioblastoma (GBM) is an aggressive malignant brain-tumor that invades adjacent normal brain tissue. Unlike other solid tumors, GBM is infiltrated by various normal brain cells.
Methods:
We analyzed tumor invasion in the murine GSC005 glioma model using both immunodeficient and immunocompetent mice, focusing on the role of host-intrinsic and therapeutic interferon signaling in regulating glioblastoma (GBM) invasion.
Results:
In this study, we observed that mouse GBM tumor GSC005 grown in immunodeficient (RAG1-KO, NSG) mice exhibited a more invasive phenotype compared to those in immunocompetent C57BL/6J mice. Immunofluorescence staining revealed the presence of vimentin + and GFAP + cells at the tumor-border interface. Bulk mRNA-seq analysis showed that GSC005 tumors in NSG mice displayed an upregulated mesenchymal signature, characterized by epithelial-to-mesenchymal transition (EMT), and downregulation of type-I and type-II interferon signaling. Our data further suggests that host-intrinsic and therapeutic type-I interferon promotes, while type-II interferon inhibits, the GBM mesenchymal signature. CD73, a key regulator of the EMT process, was found to be upregulated in GSC005 tumors in NSG mice compared to C57BL/6J mice. Mechanistic studies revealed that type-I interferon increases CD73 expression in both tumor and stromal cells, such as tumor-associated astrocytes (mAS), while type-II interferon suppresses CD73 in mAS. Functional assays indicated that CD73 modulates both type-I and type-II interferon signaling-mediated GBM invasion.
Conclusion:
These findings suggest that therapies inducing type-I or type-II interferon signaling in GBM may reciprocally regulate CD73-mediated mesenchymal transitions, impacting GBM invasion.
