CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironment

Novak, Metka (avtor), Koprivnikar Krajnc, Miha (avtor), Hrastar, Barbara (avtor), Breznik, Barbara (avtor), Majc, Bernarda (avtor), Mlinar, Mateja (avtor), Rotter, Ana (avtor), Porčnik, Andrej (avtor), Mlakar, Jernej (avtor), Stare, Katja (avtor), Pestell, Richard G. (avtor), Lah Turnšek, Tamara (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: CCL5, CCR5, chemokines, glioblastoma, invasion, maraviroc, mesenchymal stem cells
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 20 str.
• Številčenje: Vol. 21, iss. 12, art. 4199
• PID: 20.500.12556/RUL-133933
• UDK: 577
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms21124199
• COBISS.SI-ID: 19416067
• Datum objave v RUL: 20.12.2021

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 12.06.2020

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: glioblastom, kemokini, tumorsko mikrookolje, invazija