20.500.12556/DiRROS-19518 CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironment Abstract The chemokine CCL5/RANTES is a versatile inflammatory mediator, which interacts with the receptor CCR5, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which CCL5 expression correlates with shorter patient survival. Using immunohistochemistry, we identified CCL5 and CCR5 in a series of glioblastoma samples and cells, including glioblastoma stem cells. CCL5 and CCR5 gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on CCL5-induced CCR5 signaling and is strongly inhibited by the small molecule CCR5 antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release CCR5 ligands. In support of this model, we detected CCL5 and CCR5 in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found CCR5 expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves CCR5 and CCL5, contributing to glioblastoma invasion, suggesting the CCL5/CCR5 axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc. CCL5 CCR5 chemokines glioblastoma invasion maraviroc mesenchymal stem cells glioblastom kemokini tumorsko mikrookolje invazija true false true Angleški jezik Slovenski jezik Neznano 2024-07-19 03:42:42 2024-07-22 10:05:15 2024-07-23 03:38:07 0000-00-00 00:00:00 2020 0 0 Nasl. z nasl. zaslona; Opis vira z dne 12. 6. 2020; str. 1-20 iss. 12 Vol. 21 12 Jun. 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2020-06-12 577 1422-0067 19416067 https://www.mdpi.com/1422-0067/21/12/4199 1 6cfacbce-455f-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26922 Nacionalni inštitut za biologijo 0 0 0