TY - JOUR TI - P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression AU - Yeini, Eilam AU - Ofek, Paula AU - Pozzi, Sabina AU - Albeck, Nitzan AU - Ben-Shushan, Dikla AU - Tiram, Galia AU - Golan, Sapir AU - Kleiner, Ron AU - Sheinin, Ron AU - Israeli Dangoor, Sahar AU - Reich-Zeliger, Shlomit AU - Grossman, Rachel AU - Ram, Zvi AU - Brem, Henry AU - Hyde, Thomas M. AU - Magod, Prerna AU - Friedmann-Morvinski, Dinorah AU - Madi, Asaf AU - Satchi-Fainaro, Ronit T2 - Nature Communications AB - 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 suppressĀ the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy. DA - 2021/03/26/ PY - 2021 DO - 10.1038/s41467-021-22186-0 DP - www.nature.com VL - 12 IS - 1 SP - 1912 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-021-22186-0 Y2 - 2021/03/26/17:44:05 ER -