TGF-β1 activates neutrophil signaling and gene expression but not migration.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
26
05
2023
accepted:
17
08
2023
medline:
11
9
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
Tumor-associated neutrophils are found in many types of cancer and are often reported to contribute to negative outcomes. The presence of transforming growth factor-beta (TGF-β) in the tumor microenvironment reportedly contributes to the skewing of neutrophils to a more pro-tumor phenotype. The effects of TGF-β on neutrophil signaling and migration are, however, unclear. We sought to characterize TGF-β signaling in both primary human neutrophils and the neutrophil-like cell line HL-60 and determine whether it directly induces neutrophil migration. We found that TGF-β1 does not induce neutrophil chemotaxis in transwell or underagarose migration assays. TGF-β1 does activate canonical signaling through SMAD3 and noncanonical signaling through ERK1/2 in neutrophils in a time- and dose-dependent manner. Additionally, TGF-β1 present in the tumor-conditioned media (TCM) of invasive breast cancer cells results in SMAD3 activation. We discovered that TCM induces neutrophils to secrete leukotriene B4 (LTB4), which is a lipid mediator important for amplifying the range of neutrophil recruitment. However, TGF-β1 alone does not induce secretion of LTB4. RNA-sequencing revealed that TGF-β1 and TCM alter gene expression in HL-60 cells, including the mRNA levels of the pro-tumor oncostatin M (OSM) and vascular endothelial growth factor A (VEGFA). These new insights into the role and impact of TGF-β1 on neutrophil signaling, migration, and gene expression have significant implications in the understanding of the changes in neutrophils that occur in the tumor microenvironment.
Identifiants
pubmed: 37682817
doi: 10.1371/journal.pone.0290886
pii: PONE-D-23-16254
pmc: PMC10490904
doi:
Substances chimiques
Transforming Growth Factor beta1
0
Vascular Endothelial Growth Factor A
0
Leukotriene B4
1HGW4DR56D
Transforming Growth Factor beta
0
Culture Media, Conditioned
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0290886Subventions
Organisme : NIAID NIH HHS
ID : R01 AI152517
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright: © 2023 Hein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Pharmacol Exp Ther. 2015 May;353(2):340-50
pubmed: 25736418
Cancers (Basel). 2019 Apr 19;11(4):
pubmed: 31010242
Dev Cell. 2012 May 15;22(5):1079-91
pubmed: 22542839
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
Nature. 2015 Dec 17;528(7582):413-7
pubmed: 26649828
J Clin Invest. 2010 Apr;120(4):1151-64
pubmed: 20237412
Cancers (Basel). 2022 Jan 21;14(3):
pubmed: 35158807
Immunol Rev. 2016 Sep;273(1):312-28
pubmed: 27558343
JCI Insight. 2019 Jul 25;5:
pubmed: 31343990
Cell. 2019 Mar 7;176(6):1248-1264
pubmed: 30849371
J Biol Chem. 1997 Oct 31;272(44):28107-15
pubmed: 9346966
Arthritis Rheum. 2004 May;50(5):1430-6
pubmed: 15146412
Cancer Res. 2001 Jul 15;61(14):5407-14
pubmed: 11454684
J Biol Chem. 2000 Jun 30;275(26):20146-56
pubmed: 10867029
Blood. 1999 Feb 15;93(4):1413-21
pubmed: 9949186
Can J Physiol Pharmacol. 1989 May;67(5):456-64
pubmed: 2548691
Int J Biol Sci. 2023 Feb 21;19(5):1352-1368
pubmed: 37056931
Clin Cancer Res. 2019 Mar 15;25(6):1957-1969
pubmed: 30482778
J Biol Chem. 2012 Oct 19;287(43):36593-608
pubmed: 22927430
Cancer Manag Res. 2018 Dec 05;10:6685-6693
pubmed: 30584363
Cancer Res. 2016 Mar 15;76(6):1367-80
pubmed: 26759232
Cancer Cell. 2019 Sep 16;36(3):319-336.e7
pubmed: 31526760
BMC Mol Biol. 2005 Feb 18;6:4
pubmed: 15720708
J Leukoc Biol. 2019 Mar;105(3):449-462
pubmed: 30549315
Tissue Antigens. 1974;4(4):269-74
pubmed: 4415728
Sci Signal. 2016 Dec 13;9(458):ra122
pubmed: 27965424
Nat Rev Immunol. 2013 Mar;13(3):159-75
pubmed: 23435331
Sci Transl Med. 2016 Oct 19;8(361):361ra138
pubmed: 27798263
Nucleic Acids Res. 2022 Jan 7;50(D1):D687-D692
pubmed: 34788843
PLoS Biol. 2021 Jul 7;19(7):e3001271
pubmed: 34232954
J Biol Chem. 1991 Dec 5;266(34):23048-52
pubmed: 1744101
Nat Rev Cancer. 2020 Sep;20(9):485-503
pubmed: 32694624
Nature. 1976 Oct 14;263(5578):594-5
pubmed: 1086432
Nature. 2013 Jun 20;498(7454):371-5
pubmed: 23708969
Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30
pubmed: 22992590
J Immunol. 1994 Mar 1;152(5):2456-66
pubmed: 8133057
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10669-74
pubmed: 9380693
Methods Cell Biol. 2019;149:31-56
pubmed: 30616826
J Biol Chem. 1999 Nov 19;274(47):33412-8
pubmed: 10559222
Cell. 2008 Jul 25;134(2):215-30
pubmed: 18662538
Annu Rev Cell Dev Biol. 2005;21:247-69
pubmed: 16212495
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nucleic Acids Res. 2019 May 7;47(8):e47
pubmed: 30783653
Cell Rep. 2015 Feb 3;10(4):562-73
pubmed: 25620698
J Lipid Res. 2015 Aug;56(8):1386-402
pubmed: 25838312
Expert Opin Ther Targets. 2020 May;24(5):427-438
pubmed: 32228232
Clin Exp Immunol. 2007 Jul;149(1):155-61
pubmed: 17403059
J Biol Chem. 1997 Jan 31;272(5):2896-900
pubmed: 9006934
Cancer Cell. 2009 Sep 8;16(3):183-94
pubmed: 19732719
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Invest Ophthalmol Vis Sci. 2022 Apr 1;63(4):2
pubmed: 35377925
Immunity. 2021 Jul 13;54(7):1377-1391
pubmed: 34260886
J Biol Chem. 1991 Jan 15;266(2):1092-100
pubmed: 1985937
Oncology. 2005;69 Suppl 3:4-10
pubmed: 16301830
Cancer Cell. 2011 Sep 13;20(3):300-14
pubmed: 21907922
Mol Pharmacol. 2002 Jul;62(1):65-74
pubmed: 12065756
J Clin Invest. 2013 Jul 1;:
pubmed: 23863628
Exp Cell Res. 1980 Apr;126(2):494-8
pubmed: 6988226
Cold Spring Harb Perspect Biol. 2017 Feb 1;9(2):
pubmed: 27864313
Nucleic Acids Res. 1995 Dec 11;23(23):4907-12
pubmed: 8532536
Nat Cell Biol. 2022 Jul;24(7):1019-1028
pubmed: 35739317
Physiol Rev. 2019 Apr 1;99(2):1223-1248
pubmed: 30758246
Front Immunol. 2021 Apr 12;12:659996
pubmed: 33912188
J Biol Chem. 1997 Oct 31;272(44):27678-85
pubmed: 9346908
J Invest Dermatol. 2016 Oct;136(10):2041-2048
pubmed: 27251789
ISRN Inflamm. 2013 Dec 08;2013:512103
pubmed: 24381786
Rev Physiol Biochem Pharmacol. 2003;149:39-52
pubmed: 12811586
Nat Rev Cancer. 2016 Jul;16(7):431-46
pubmed: 27282249
Asian Pac J Cancer Prev. ;18(10):2689-2693
pubmed: 29072393
Oncoimmunology. 2016 Sep 13;5(11):e1232221
pubmed: 27999744
Cancer Res. 2005 Oct 1;65(19):8896-904
pubmed: 16204061
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6805-9
pubmed: 1650483