PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype.

Autor: Sturniolo I; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary., Váróczy C; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; National Academy of Scientist Education, 4032 Debrecen, Hungary., Regdon Z; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Mázló A; Department of Immunology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Muzsai S; Department of Immunology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, University of Debrecen, 4032 Debrecen, Hungary., Bácsi A; Department of Immunology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; HUN-REN-DE Allergology Research Group, 4032 Debrecen, Hungary., Intili G; Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy., Hegedűs C; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Boothby MR; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37235, USA., Holechek J; Agilent Technologies, Wilmington, DE 19808, USA., Ferraris D; Department of Chemistry, McDaniel College, Westminster, MD 21157, USA., Schüler H; Center for Molecular Protein Science, Department of Chemistry, Lund University, 22100 Lund, Sweden., Virág L; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.; HUN-REN-DE Cell Biology and Signaling Research Group, 4032 Debrecen, Hungary.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Mar 22; Vol. 25 (7). Date of Electronic Publication: 2024 Mar 22.
DOI: 10.3390/ijms25073601
Abstrakt: 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.
Databáze: MEDLINE
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