PMID- 29531019
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20210217
IS  - 1535-9484 (Electronic)
IS  - 1535-9476 (Print)
IS  - 1535-9476 (Linking)
VI  - 17
IP  - 6
DP  - 2018 Jun
TI  - Paclitaxel Treatment and Proprotein Convertase 1/3 (PC1/3) Knockdown in 
      Macrophages is a Promising Antiglioma Strategy as Revealed by Proteomics and 
      Cytotoxicity Studies.
PG  - 1126-1143
LID - 10.1074/mcp.RA117.000443 [doi]
AB  - 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.
CI  - (c) 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Duhamel, Marie
AU  - Duhamel M
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France; marie.duhamel@univ-lille1.fr.
FAU - Rose, Melanie
AU  - Rose M
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
AD  -  section signOncovet Clinical Research (OCR), SIRIC ONCOLille, Villeneuve d'Ascq, France.
FAU - Rodet, Franck
AU  - Rodet F
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
FAU - Murgoci, Adriana Natalia
AU  - Murgoci AN
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
AD  -  section sign section signInstitute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, 
      Slovak Republic.
FAU - Zografidou, Lea
AU  - Zografidou L
AD  -  paragraph signJohannes Gutenberg-Universitat Mainz, Johann-Joachim-Becher-Weg 15, D-55128 
      Mainz, Germany.
FAU - Regnier-Vigouroux, Anne
AU  - Regnier-Vigouroux A
AD  -  paragraph signJohannes Gutenberg-Universitat Mainz, Johann-Joachim-Becher-Weg 15, D-55128 
      Mainz, Germany.
FAU - Vanden Abeele, Fabien
AU  - Vanden Abeele F
AD  -  ||Inserm U-1003, Equipe labellisee par la Ligue Nationale contre le cancer, 
      Laboratory of Excellence, Ion Channels Science and Therapeutics, Universite Lille 
      1, Cite Scientifique, 59655 Villeneuve d'Ascq, France.
FAU - Kobeissy, Firas
AU  - Kobeissy F
AD  - **Department of Biochemistry and Molecular Genetics, Faculty of Medicine, 
      American University of Beirut, 1107 2020 Beirut, Lebanon.
FAU - Nataf, Serge
AU  - Nataf S
AD  - double daggerdouble daggerInserm U-1060, CarMeN Laboratory, Banque de Tissus et de Cellules des Hospices 
      Civils de Lyon, Universite Lyon-1, Hopital Edouard Herriot, 69437 Lyon cedex 03, 
      France.
FAU - Pays, Laurent
AU  - Pays L
AD  - double daggerdouble daggerInserm U-1060, CarMeN Laboratory, Banque de Tissus et de Cellules des Hospices 
      Civils de Lyon, Universite Lyon-1, Hopital Edouard Herriot, 69437 Lyon cedex 03, 
      France.
FAU - Wisztorski, Maxence
AU  - Wisztorski M
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
FAU - Cizkova, Dasa
AU  - Cizkova D
AD  -  section sign section signInstitute of Neuroimmunology, Slovak Academy of Sciences, 845 10, Bratislava, 
      Slovak Republic.
FAU - Fournier, Isabelle
AU  - Fournier I
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
FAU - Salzet, Michel
AU  - Salzet M
AD  - From the double daggerInserm U-1192, Laboratoire de Proteomique, Reponse Inflammatoire, 
      Spectrometrie de Masse (PRISM), Universite Lille 1, Cite Scientifique, 59655 
      Villeneuve D'Ascq, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180312
PL  - United States
TA  - Mol Cell Proteomics
JT  - Molecular & cellular proteomics : MCP
JID - 101125647
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Cytokines)
RN  - EC 3.4.21.93 (Proprotein Convertase 1)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Brain Neoplasms/metabolism/*therapy
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Glioma/metabolism/*therapy
MH  - Macrophages/drug effects/metabolism
MH  - Paclitaxel/*pharmacology
MH  - Proprotein Convertase 1/*genetics
MH  - Proteomics
MH  - Rats
PMC - PMC5986247
OTO - NOTNLM
OT  - Calcium Signaling*
OT  - Cancer therapeutics
OT  - Exosomes
OT  - Immunology*
OT  - Paclitaxel
OT  - Secretome
OT  - glioma
OT  - macrophages
OT  - proprotein convertase 1/3
OT  - proteomics
EDAT- 2018/03/14 06:00
MHDA- 2019/05/09 06:00
PMCR- 2019/06/01
CRDT- 2018/03/14 06:00
PHST- 2017/11/01 00:00 [received]
PHST- 2018/03/10 00:00 [revised]
PHST- 2018/03/14 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2018/03/14 06:00 [entrez]
PHST- 2019/06/01 00:00 [pmc-release]
AID - S1535-9476(20)32236-2 [pii]
AID - RA117.000443 [pii]
AID - 10.1074/mcp.RA117.000443 [doi]
PST - ppublish
SO  - Mol Cell Proteomics. 2018 Jun;17(6):1126-1143. doi: 10.1074/mcp.RA117.000443. 
      Epub 2018 Mar 12.