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Editorial
. 2019 Jul;7(Suppl 3):S83.
doi: 10.21037/atm.2019.04.17.

Reactive astrocytes foster brain metastases via STAT3 signaling

Braden C McFarland  1 , Etty N Benveniste  1
Affiliations
Editorial

Reactive astrocytes foster brain metastases via STAT3 signaling

Braden C McFarland et al. Ann Transl Med. 2019 Jul.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Illustration of microenvironmental signaling events promoting brain metastasis growth. Tumor cells in the brain metastasis begin to proliferate and secrete various cytokines and growth factors including epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α), ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6). These factors then act on the surrounding astrocytes, promoting the RA phenotype. These activated RA express PD-L1 on the surface, which directly binds to T-cells to prevent activation. Additionally, the RA secrete factors including vascular endothelial growth factor-A (VEGF-A), lipocalin-2, tissue inhibitor of metalloproteinases-1 (TIMP-1) and macrophage migration inhibitory factor (MIF), which have direct effects on immune cells. CD8+ T-cells have reduced CD44 (activation marker) expression and are prevented from infiltrating the tumor mass. Macrophages/microglia are polarized to an immunosuppressive M2 phenotype, displaying expression of CD74 and midkine. These events lead to an immunosuppressive microenvironment that allows for increased growth of the tumor within the brain.
See this image and copyright information in PMC

Comment on

  • STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.
    Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martínez L, Martínez-Saez E, Ramón Y Cajal S, Megías D, Hernández-Encinas E, Blanco-Aparicio C, Martínez L, Zarzuela E, Muñoz J, Fustero-Torre C, Piñeiro-Yáñez E, Hernández-Laín A, Bertero L, Poli V, Sanchez-Martinez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M. Priego N, et al. Nat Med. 2018 Jul;24(7):1024-1035. doi: 10.1038/s41591-018-0044-4. Epub 2018 Jun 11. Nat Med. 2018. PMID: 29892069

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