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PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype
by
Szabolcs Muzsai
, Attila Bácsi
, Dana Ferraris
, László Virág
, Giorgia Intili
, Isotta Sturniolo
, Zsolt Regdon
, Jacob Holechek
, Herwig Schüler
, Mark R. Boothby
, Csongor Váróczy
, Anett Mázló
, Csaba Hegedűs
in
Animals
/ Antigens
/ Basic Medicine
/ Breast cancer
/ Breast Neoplasms
/ Cancer
/ Cancer and Oncology
/ Cancer och onkologi
/ Cancer therapies
/ Cell and Molecular Biology
/ Cell Differentiation
/ Cell- och molekylärbiologi
/ Clinical Medicine
/ Cytotoxicity
/ Enzymes
/ Female
/ Gene expression
/ Genes
/ Genetic aspects
/ Genotype & phenotype
/ Humans
/ Immune system
/ Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
/ Immunology in the Medical Area (including Cell and Immunotherapy)
/ Immunotherapy
/ Klinisk medicin
/ Lymphocytes
/ Macrophages
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Knockout
/ Monosaccharides
/ Poly(ADP-ribose) Polymerases
/ Sugars
/ Tamoxifen
/ Tumor-Associated Macrophages
/ Tumors
2024
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PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype
by
Szabolcs Muzsai
, Attila Bácsi
, Dana Ferraris
, László Virág
, Giorgia Intili
, Isotta Sturniolo
, Zsolt Regdon
, Jacob Holechek
, Herwig Schüler
, Mark R. Boothby
, Csongor Váróczy
, Anett Mázló
, Csaba Hegedűs
in
Animals
/ Antigens
/ Basic Medicine
/ Breast cancer
/ Breast Neoplasms
/ Cancer
/ Cancer and Oncology
/ Cancer och onkologi
/ Cancer therapies
/ Cell and Molecular Biology
/ Cell Differentiation
/ Cell- och molekylärbiologi
/ Clinical Medicine
/ Cytotoxicity
/ Enzymes
/ Female
/ Gene expression
/ Genes
/ Genetic aspects
/ Genotype & phenotype
/ Humans
/ Immune system
/ Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
/ Immunology in the Medical Area (including Cell and Immunotherapy)
/ Immunotherapy
/ Klinisk medicin
/ Lymphocytes
/ Macrophages
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Knockout
/ Monosaccharides
/ Poly(ADP-ribose) Polymerases
/ Sugars
/ Tamoxifen
/ Tumor-Associated Macrophages
/ Tumors
2024
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PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype
by
Szabolcs Muzsai
, Attila Bácsi
, Dana Ferraris
, László Virág
, Giorgia Intili
, Isotta Sturniolo
, Zsolt Regdon
, Jacob Holechek
, Herwig Schüler
, Mark R. Boothby
, Csongor Váróczy
, Anett Mázló
, Csaba Hegedűs
in
Animals
/ Antigens
/ Basic Medicine
/ Breast cancer
/ Breast Neoplasms
/ Cancer
/ Cancer and Oncology
/ Cancer och onkologi
/ Cancer therapies
/ Cell and Molecular Biology
/ Cell Differentiation
/ Cell- och molekylärbiologi
/ Clinical Medicine
/ Cytotoxicity
/ Enzymes
/ Female
/ Gene expression
/ Genes
/ Genetic aspects
/ Genotype & phenotype
/ Humans
/ Immune system
/ Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
/ Immunology in the Medical Area (including Cell and Immunotherapy)
/ Immunotherapy
/ Klinisk medicin
/ Lymphocytes
/ Macrophages
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Knockout
/ Monosaccharides
/ Poly(ADP-ribose) Polymerases
/ Sugars
/ Tamoxifen
/ Tumor-Associated Macrophages
/ Tumors
2024
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PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype
Journal Article
PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype
2024
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Overview
Cancers reprogram macrophages (MΦs) to a tumor-growth-promoting TAM (tumor-associated MΦ) phenotype that is similar to the anti-inflammatory M2 phenotype. Poly(ADP-ribose) polymerase (PARP) enzymes regulate various aspects of MΦ biology, but their role in the development of TAM phenotype has not yet been investigated. Here, we show that the multispectral PARP inhibitor (PARPi) PJ34 and the PARP14 specific inhibitor MCD113 suppress the expression of M2 marker genes in IL-4-polarized primary murine MΦs, in THP-1 monocytic human MΦs, and in primary human monocyte-derived MΦs. MΦs isolated from PARP14 knockout mice showed a limited ability to differentiate to M2 cells. In a murine model of TAM polarization (4T1 breast carcinoma cell supernatant transfer to primary MΦs) and in a human TAM model (spheroids formed from JIMT-1 breast carcinoma cells and THP-1-MΦs), both PARPis and the PARP14 KO phenotype caused weaker TAM polarization. Increased JIMT-1 cell apoptosis in co-culture spheroids treated with PARPis suggested reduced functional TAM reprogramming. Protein profiling arrays identified lipocalin-2, macrophage migration inhibitory factor, and plasminogen activator inhibitor-1 as potential (ADP-ribosyl)ation-dependent mediators of TAM differentiation. Our data suggest that PARP14 inhibition might be a viable anticancer strategy with a potential to boost anticancer immune responses by reprogramming TAMs.
Publisher
MDPI AG
Subject
/ Antigens
/ Cancer
/ Enzymes
/ Female
/ Genes
/ Humans
/ Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)
/ Immunology in the Medical Area (including Cell and Immunotherapy)
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Poly(ADP-ribose) Polymerases
/ Sugars
/ Tumor-Associated Macrophages
/ Tumors
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