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CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironment
ID Novak, Metka (Avtor), ID Koprivnikar Krajnc, Miha (Avtor), ID Hrastar, Barbara (Avtor), ID Breznik, Barbara (Avtor), ID Majc, Bernarda (Avtor), ID Mlinar, Mateja (Avtor), ID Rotter, Ana (Avtor), ID Porčnik, Andrej (Avtor), ID Mlakar, Jernej (Avtor), ID Stare, Katja (Avtor), ID Pestell, Richard G. (Avtor), ID Lah Turnšek, Tamara (Avtor)

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Izvleček
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 (dk_c)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Leto izida:2020
Status objave pri reviji:Objavljeno
Verzija članka:Založnikova različica članka
Št. strani:20 str.
Številčenje:Vol. 21, iss. 12, art. 4199
UDK:577
ISSN pri članku:1422-0067
DOI:10.3390/ijms21124199 Povezava se odpre v novem oknu
COBISS.SI-ID:19416067 Povezava se odpre v novem oknu
Datum objave v RUL:20.12.2021
Število ogledov:132
Število prenosov:47
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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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 Povezava se odpre v novem oknu

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

Gradivo je financirano iz projekta

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P1-0245
Naslov:Ekotoksiologija, toksikološka genomika in karcinogeneza

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:Z3-1870
Naslov:Vpliv mezenhimskih matičnih celic na odpornost glioblastoma na terapijo

Financer:EC - European Commission
Program financ.:Interreg
Akronim:TRANS-GLIOMA

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