Title :

The role of a proprotein convertase inhibitor in reactivation of tumor-associated macrophages and inhibition of glioma growth

Author(s) :

Rose, Melanie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Oncovet
Duhamel, Marie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Aboulouard, Soulaimane [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Kobeissy, Firas [Auteur]
McKnight Brain Institute [Gainesville] [UF|MBI]
Le Rhun, Emilie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Desmons, Annie [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Tierny, Dominique [Auteur]
Oncovet
FOURNIER, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Rodet, Franck [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Journal title :

Molecular Therapy - Oncolytics

Abbreviated title :

Mol Ther Oncolytics

Volume number :

17

Pages :

31-46

Publisher :

Elsevier

Publication date :

2020-06-26

ISSN :

2372-7705

English keyword(s) :

glioma
immunotherapy
macrophages
mass spectrometry-based proteomic
proprotein convertases
temozolomide

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Tumors are characterized by the presence of malignant and non-malignant cells, such as immune cells including macrophages, which are preponderant. Macrophages impact the efficacy of chemotherapy and may lead to drug ...
Show more >Tumors are characterized by the presence of malignant and non-malignant cells, such as immune cells including macrophages, which are preponderant. Macrophages impact the efficacy of chemotherapy and may lead to drug resistance. In this context and based on our previous work, we investigated the ability to reactivate macrophages by using a proprotein convertases inhibitor. Proprotein convertases process immature proteins into functional proteins, with several of them having a role in immune cell activation and tumorigenesis. Macrophages were treated with a peptidomimetic inhibitor targeting furin, PC1/3, PC4, PACE4, and PC5/6. Their anti-glioma activity was analyzed by mass spectrometry-based proteomics and viability assays in 2D and 3D in vitro cultures. Comparison with temozolomide, the drug used for glioma therapy, established that the inhibitor was more efficient for the reduction of cancer cell density. The inhibitor was also able to reactivate macrophages through the secretion of several immune factors with antitumor properties. Moreover, two proteins considered as good glioma patient survival indicators were also identified in 3D cultures treated with the inhibitor. Finally, we established that the proprotein convertases inhibitor has a dual role as an anti-glioma drug and anti-tumoral macrophage reactivation drug. This strategy could be used together with chemotherapy to increase therapy efficacy in glioma.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:57:27Z
2023-03-07T13:19:28Z