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Title:CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironment
Authors:ID Novak, Metka (Author)
ID Koprivnikar Krajnc, Miha (Author)
ID Hrastar, Barbara (Author)
ID Breznik, Barbara (Author)
ID Majc, Bernarda (Author)
ID Mlinar, Mateja (Author)
ID Rotter, Ana (Author)
ID Porčnik, Andrej (Author)
ID Mlakar, Jernej (Author)
ID Stare, Katja (Author)
ID Pestell, Richard G. (Author)
ID Lah Turnšek, Tamara (Author)
Files:URL URL - Source URL, visit https://www.mdpi.com/1422-0067/21/12/4199
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
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:CCL5, CCR5, chemokines, glioblastoma, invasion, maraviroc, mesenchymal stem cells
Publication status:Published
Publication version:Version of Record
Publication date:12.06.2020
Year of publishing:2020
Number of pages:str. 1-20
Numbering:Vol. 21, iss. 12
PID:20.500.12556/DiRROS-19518 New window
UDC:577
ISSN on article:1422-0067
COBISS.SI-ID:19416067 New window
Note:Nasl. z nasl. zaslona; Opis vira z dne 12. 6. 2020;
Publication date in DiRROS:22.07.2024
Views:539
Downloads:189
Metadata:XML DC-XML DC-RDF
:
NOVAK, Metka, KOPRIVNIKAR KRAJNC, Miha, HRASTAR, Barbara, BREZNIK, Barbara, MAJC, Bernarda, MLINAR, Mateja, ROTTER, Ana, PORČNIK, Andrej, MLAKAR, Jernej, STARE, Katja, PESTELL, Richard G. and LAH TURNŠEK, Tamara, 2020, CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironment. International journal of molecular sciences [online]. 2020. Vol. 21, no. 12, p. 1–20. [Accessed 23 April 2025]. Retrieved from: https://www.mdpi.com/1422-0067/21/12/4199
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
Publisher:MDPI
ISSN:1422-0067
COBISS.SI-ID:2779162 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0245-2019
Name:Ekotoksiologija, toksikološka genomika in karcinogeneza
Funder:ARIS - Slovenian Research and Innovation Agency
Project number:Z3-1870-2019
Name:Vpliv mezenhimskih matičnih celic na odpornost glioblastoma na terapijo

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Keywords:glioblastom, kemokini, tumorsko mikrookolje, invazija


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