Title :

Paclitaxel�treatment and pc1/3 knockdown in macrophages is a promising anti-glioma strategy as revealed by proteomics and cytotoxicity studies

Author(s) :

Duhamel, Marie [Auteur]
Rose, Melanie [Auteur]
Rodet, Franck [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Murgoci, Adriana-Natalia [Auteur]
Zografidou, Lea [Auteur]
Regnier-Vigouroux, Anne [Auteur]
Vanden Abeele, Fabien [Auteur]
Kobeissy, Firas [Auteur]
Nataf, Serge [Auteur]
Pays, Laurent [Auteur]
Wisztorski, Maxence [Auteur]
Cizkova, Dasa [Auteur]
FOURNIER, Isabelle [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Salzet, Michel [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Journal title :

Molecular & cellular proteomics . MCP

Abbreviated title :

Mol. Cell Proteomics

Publication date :

2018-03-12

ISSN :

1535-9484

Keyword(s) :

3
Cancer therapeutics
Exosomes
Immunology*
Secretome
glioma
macrophages
Paclitaxel
proprotein convertase 1
proteomics
Calcium Signaling*

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune ...
Show more >High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells toward a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an antitumoral phenotype. Previously, we demonstrated that macrophages secreted antitumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS. However, achieving an activation of macrophages via LPS/TLR4/Myd88-dependent pathway appears yet unfeasible in cancer patients. On the contrary, the antitumor drug Paclitaxel is also known to activate the TLR4 MyD88-dependent signaling pathway and mimics LPS action. Therefore, we evaluated if PC1/3 knock-down (KD) macrophages could be activated by Paclitaxel and efficient against glioma. We report here that such a treatment of PC1/3 KD macrophages drove to the overexpression of proteins mainly involved in cytoskeleton rearrangement. In support of this finding, we found that these cells exhibited a Ca(2+) increase after Paclitaxel treatment. This is indicative of a possible depolymerization of microtubules and may therefore reflect an activation of inflammatory pathways in macrophages. In such a way, we found that PC1/3 KD macrophages displayed a repression of the anti-inflammatory pathway STAT3 and secreted more pro-inflammatory cytokines. Extracellular vesicles isolated from these PC1/3 KD cells inhibited glioma growth. Finally, the supernatant collected from the coculture between glioma cells and PC1/3 KD macrophages contained more antitumoral factors. These findings unravel the potential value of a new therapeutic strategy combining Paclitaxel and PC1/3 inhibition to switch macrophages toward an antitumoral immunophenotype.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Inserm
Université de Lille

Collections :

• Physiologie Cellulaire (PHYCELL) - U1003
• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:58:33Z