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

Abstract

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.

Keywords

glioblastom;kemokini;tumorsko mikrookolje;invazija;CCL5;CCR5;chemokines;glioblastoma;invasion;maraviroc;mesenchymal stem cells;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: NIB - National Institute of Biology
UDC: 577
COBISS: 19416067 Link will open in a new window
ISSN: 1422-0067
Views: 14
Downloads: 5
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: glioblastom;kemokini;tumorsko mikrookolje;invazija;
Type (COBISS): Article
Source comment: Nasl. z nasl. zaslona; Opis vira z dne 12. 6. 2020;
Pages: str. 1-20
Volume: ǂVol. ǂ21
Issue: ǂiss. ǂ12
Chronology: 12 Jun. 2020
DOI: 10.3390/ijms21124199
ID: 24574211