Connexion
S'inscrire
Réinitialiser le mot de passe
Publier & Distribuer
Solutions d'édition
Solutions de distribution
Thèmes
Architecture et design
Arts
Business et économie
Chimie
Chimie industrielle
Droit
Géosciences
Histoire
Informatique
Ingénierie
Intérêt général
Linguistique et sémiotique
Littérature
Mathématiques
Musique
Médecine
Pharmacie
Philosophie
Physique
Sciences bibliothécaires et de l'information, études du livre
Sciences des matériaux
Sciences du vivant
Sciences sociales
Sport et loisirs
Théologie et religion
Études classiques et du Proche-Orient ancient
Études culturelles
Études juives
Publications
Journaux
Livres
Comptes-rendus
Éditeurs
Blog
Contact
Chercher
EUR
USD
GBP
Français
English
Deutsch
Polski
Español
Français
Italiano
Panier
Home
Journaux
Radiology and Oncology
Édition 53 (2019): Edition 4 (December 2019)
Accès libre
Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme
Miha Koprivnikar Kranjc
Miha Koprivnikar Kranjc
,
Metka Novak
Metka Novak
,
Richard G. Pestell
Richard G. Pestell
et
Tamara T. Lah
Tamara T. Lah
| 20 nov. 2019
Radiology and Oncology
Édition 53 (2019): Edition 4 (December 2019)
À propos de cet article
Article précédent
Article suivant
Résumé
Article
Figures et tableaux
Références
Auteurs
Articles dans cette édition
Aperçu
PDF
Citez
Partagez
Article Category:
Review
Publié en ligne:
20 nov. 2019
Pages:
397 - 406
Reçu:
14 août 2019
Accepté:
15 oct. 2019
DOI:
https://doi.org/10.2478/raon-2019-0057
© 2019 Miha Koprivnikar Kranjc, Metka Novak, Richard G. Pestell, Tamara T. Lah, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Figure 1
Chemokine CCL5 promiscuous binding to receptors. A variety of chemokine-receptors are interacting with CCL5/CCR5 in the signalling axis: (A) in addition to the cognate receptor CCR5, CCL5 binds also to CCR3 and CCR1. Non-conventional receptors are GPR75 and CD44. (B) The chemokines which bind to CCR5 are also CCL5, CCL4 and CCL3.
Figure 2
Phosphatidylinositol 3-kinase (PI3K)/pAkt-kinase pathway as a central CCL5/CCR5 signalling cascade in cancer cells. Upon CCL5 binding to its cognate receptor CCR5, primarily the PI3K/Akt pathway is triggered. This favours the phosphorylation of PIP2 to PIP3, a secondary messenger responsible for the activation of the Akt kinase, which in turn phosphorylates several downstream effectors. This causes the inhibition of pro-apoptotic effectors and the upregulation of survival genes. Another target of PI3K is the mammalian target of rapamycin complex 1 (mTORC1), which also activates the Akt kinase. However, it has also been shown that a secondary intracellular target, Focal Adhesion kinase (FAK) binding-SRC kinase complex can be activated, resulting in additional PI3K activation (in prostate cancer62).
Figure 3
CCL5-CCR5 system and microglia polarization. The pharmacological blockade of CCR5 with maraviroc prevents the activity of glioblastoma-associated anti-inflammatory microglia M2 phenotype in and induces (green arrow) the conversion to prevailing pro-inflammatory M1 microglia phenotype.
Figure 4
CCL5 and CCR5 in Glioblastoma microenvironment. (A) Fluorescence immunohistochemical labelling of CCR5 in glioblastoma associated macrophages. Macrophages in the tumour section were immuno-fluorescently labelled to detect antigen CD68 (marker for macrophages), as well as CCR5 expressions in glioblastoma tissue samples of glioblastoma patient. Nuclei were stained with DAPI (blue), CD68 with Alexa Fluor 546 (red) and CCR5 with Alexa Fluor 488 (green) dye. CCR5 is expressed in macrophages, shown in yellow in merged pictures. 40x magnification was used. (B) CCL5 is expressed in proximity to MSC on glioblastoma tissue slide. Immunofluorescence images of GB tissue slides, labelled for CD105 marker of Mesenchymal stem cells (green positive cells) and CCL5 (red). We observe selective localisation of CCL5 in glioblastoma cells and colonalization in the fraction of mesenchymal stem cells, expressing CCL5. This indicates the involvement of MSCs in the CCL5/CCR5 signalling in glioblastoma. CCL5 was also expressed in glioblastoma cells.
Aperçu