P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression

Eilam Yeini, Paula Ofek, Sabina Pozzi, Nitzan Albeck, Dikla Ben-Shushan, Galia Tiram, Sapir Golan, Ron Kleiner, Ron Sheinin, Sahar Israeli Dangoor, Shlomit Reich-Zeliger, Rachel Grossman, Zvi Ram, Henry Brem, Thomas M. Hyde, Prerna Magod, Dinorah Friedmann-Morvinski, Asaf Madi and Ronit Satchi-Fainaro ()
Additional contact information
Eilam Yeini: Sackler Faculty of Medicine, Tel Aviv University
Paula Ofek: Sackler Faculty of Medicine, Tel Aviv University
Sabina Pozzi: Sackler Faculty of Medicine, Tel Aviv University
Nitzan Albeck: Sackler Faculty of Medicine, Tel Aviv University
Dikla Ben-Shushan: Sackler Faculty of Medicine, Tel Aviv University
Galia Tiram: Sackler Faculty of Medicine, Tel Aviv University
Sapir Golan: Sackler Faculty of Medicine, Tel Aviv University
Ron Kleiner: Sackler Faculty of Medicine, Tel Aviv University
Ron Sheinin: Sackler Faculty of Medicine, Tel Aviv University
Sahar Israeli Dangoor: Sackler Faculty of Medicine, Tel Aviv University
Shlomit Reich-Zeliger: Weizmann Institute of Science
Rachel Grossman: Tel Aviv Sourasky Medical Center
Zvi Ram: Tel Aviv Sourasky Medical Center
Henry Brem: Johns Hopkins University School of Medicine
Thomas M. Hyde: Lieber Institute for Brain Development, Johns Hopkins Medical Campus
Prerna Magod: George S. Wise Faculty of Life Sciences, Sherman Building, Tel Aviv University
Dinorah Friedmann-Morvinski: Sagol School of Neurosciences, Tel Aviv University
Asaf Madi: Sackler Faculty of Medicine, Tel Aviv University
Ronit Satchi-Fainaro: Sackler Faculty of Medicine, Tel Aviv University

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract Glioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. However, the reciprocal mechanisms by which GB cells alter microglia/macrophages behavior are not fully understood. We propose that these mechanisms involve adhesion molecules such as the Selectins family. These proteins are involved in immune modulation and cancer immunity. We show that P-selectin mediates microglia-enhanced GB proliferation and invasion by altering microglia/macrophages activation state. We demonstrate these findings by pharmacological and molecular inhibition of P-selectin which leads to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophage function and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22186-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22186-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22186-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().