Increased Density of Growth Differentiation Factor-15+ Immunoreactive M1/M2 Macrophages in Prostate Cancer of Different Gleason Scores Compared with Benign Prostate Hyperplasia.
GDF-15
Gleason scores
benign prostatic hyperplasia
biomarker
innervation
lymphocytes
macrophages
prostate cancer
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
22 Sep 2022
22 Sep 2022
Historique:
received:
02
08
2022
revised:
15
09
2022
accepted:
19
09
2022
entrez:
14
10
2022
pubmed:
15
10
2022
medline:
15
10
2022
Statut:
epublish
Résumé
Although growth differentiation factor-15 (GDF-15) is highly expressed in PCa, its role in the development and progression of PCa is unclear. The present study aims to determine the density of GDF-15+ cells and immune cells (M1-/M2 macrophages [MΦ], lymphocytes) in PCa of different Gleason scores (GS) compared to BPH. Immunohistochemistry and double immunofluorescence were performed on paraffin-embedded human PCa and BPH biopsies with antibodies directed against GDF-15, CD68 (M1 MΦ), CD163 (M2 MΦ), CD4, CD8, CD19 (T /B lymphocytes), or PD-L1. PGP9.5 served as a marker for innervation and neuroendocrine cells. GDF-15+ cell density was higher in all GS than in BPH. CD68+ MΦ density in GS9 and CD163+ MΦ exceeded that in BPH. GDF-15+ cell density correlated significantly positively with CD68+ or CD163+ MΦ density in extratumoral areas. Double immunoreactive GDF-15+/CD68+ cells were found as transepithelial migrating MΦ. Stromal CD68+ MΦ lacked GDF-15+. The area of PGP9.5+ innervation was higher in GS9 than in BPH. PGP9.5+ cells, occasionally copositive for GDF-15+, also occurred in the glandular epithelium. In GS6, but not in BPH, GDF-15+, PD-L1+, and CD68+ cells were found in epithelium within luminal excrescences. The degree of extra-/intra-tumoral GDF-15 increases in M1/M2Φ is proposed to be useful to stratify progredient malignancy of PCa. GDF-15 is a potential target for anti-tumor therapy.
Identifiants
pubmed: 36230513
pii: cancers14194591
doi: 10.3390/cancers14194591
pmc: PMC9578283
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Open Access Publication Fund of Philipps-Universität Marburg with the support of the Deutsche Forschungsgemeinschaft
ID : DFG, German Research Foundation
Références
Br J Cancer. 2003 Apr 7;88(7):1101-4
pubmed: 12671711
Prostate. 2001 Feb 1;46(2):108-15
pubmed: 11170138
Trends Cancer. 2017 Dec;3(12):812-815
pubmed: 29198437
Prostate. 2020 May;80(6):500-507
pubmed: 32077525
Am J Cancer Res. 2017 May 01;7(5):1016-1036
pubmed: 28560055
Cancer Discov. 2019 Jun;9(6):702-710
pubmed: 30944117
Oncotarget. 2017 Mar 28;8(13):21526-21538
pubmed: 28423526
J Histochem Cytochem. 2000 Aug;48(8):1121-30
pubmed: 10898805
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3410-5
pubmed: 12624183
J Comp Neurol. 2001 Oct 8;439(1):32-45
pubmed: 11579380
J Biol Chem. 1998 May 29;273(22):13760-7
pubmed: 9593718
Cancer Cell. 2005 May;7(5):411-23
pubmed: 15894262
Front Immunol. 2020 May 19;11:951
pubmed: 32508832
Cell Metab. 2018 Sep 4;28(3):353-368
pubmed: 30184485
Pathobiology. 2020;87(2):87-99
pubmed: 32045912
Mod Pathol. 2018 Jan;31(S1):S122-132
pubmed: 29297494
Cancer Sci. 2019 May;110(5):1564-1572
pubmed: 30861269
Front Oncol. 2021 Jul 01;11:710899
pubmed: 34277455
Arch Pathol Lab Med. 1985 Jul;109(7):607-12
pubmed: 2409946
Biosci Rep. 2021 Jan 29;41(1):
pubmed: 33289508
PLoS One. 2020 Jun 5;15(6):e0233846
pubmed: 32502202
Syst Biol Reprod Med. 2021 Oct;67(5):354-365
pubmed: 34180329
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
J Neuroimmunol. 2019 Jul 15;332:99-111
pubmed: 30999218
Cells. 2021 Nov 19;10(11):
pubmed: 34831468
Cytokine Growth Factor Rev. 2022 Apr;64:71-83
pubmed: 34836750
J Biol Chem. 2017 Feb 3;292(5):2021-2031
pubmed: 28003366
Brain Res. 1983 Nov 14;278(1-2):224-8
pubmed: 6640310
Cancer Manag Res. 2019 Apr 02;11:2653-2661
pubmed: 31114328
JCI Insight. 2018 Sep 20;3(18):
pubmed: 30232274
PLoS One. 2015 Apr 08;10(4):e0122249
pubmed: 25853582
J Cancer. 2017 Aug 25;8(15):2915-2923
pubmed: 28928882
Prostate. 2006 May 1;66(6):651-9
pubmed: 16388506
Clin Cancer Res. 2006 Jan 1;12(1):89-96
pubmed: 16397029
Life Sci Alliance. 2018 May 29;1(2):
pubmed: 30090875
Nat Rev Urol. 2020 Feb;17(2):119-130
pubmed: 31937919
Investig Clin Urol. 2020 Jul;61(4):411-418
pubmed: 32665998
Clin Cancer Res. 2020 Feb 15;26(4):970-977
pubmed: 31615933
Clin Exp Metastasis. 2020 Aug;37(4):451-464
pubmed: 32504264
Carcinogenesis. 2020 Aug 12;41(8):1074-1082
pubmed: 32614434
Biochem Pharmacol. 2013 Mar 1;85(5):597-606
pubmed: 23220538
Cell Mol Immunol. 2020 Aug;17(8):807-821
pubmed: 32612154
Cancer. 1992 Jul 1;70(1 Suppl):254-68
pubmed: 1350941
Arch Pathol Lab Med. 1988 Nov;112(11):1097-9
pubmed: 3178423
Biochem Res Int. 2012;2012:123706
pubmed: 22811913
In Vivo. 2018 Jan-Feb;32(1):151-158
pubmed: 29275313
Prostate Cancer Prostatic Dis. 2012 Dec;15(4):320-8
pubmed: 22370725
J Med Life. 2017 Jan-Mar;10(1):5-12
pubmed: 28255369
Cancer Res. 2015 May 1;75(9):1777-81
pubmed: 25795709
J Immunol Res. 2018 Feb 5;2018:2584243
pubmed: 29651440
Prostate. 2015 Feb 15;75(3):255-65
pubmed: 25327758
Endocr Rev. 2020 Aug 1;41(4):
pubmed: 32310257
Front Cell Dev Biol. 2020 Dec 17;8:601738
pubmed: 33392191
Nat Immunol. 2007 Mar;8(3):239-45
pubmed: 17304234
JAMA Oncol. 2019 Aug 01;5(8):1195-1204
pubmed: 31318407
World J Surg Oncol. 2021 Jul 16;19(1):215
pubmed: 34271938
Am J Surg Pathol. 2017 Apr;41(4):e1-e7
pubmed: 28177964
Endocr Relat Cancer. 2019 Jan 1;26(4):411-423
pubmed: 30689542
Prostate. 2007 Dec 1;67(16):1761-9
pubmed: 17929277
Sci Transl Med. 2016 Mar 2;8(328):328rv4
pubmed: 26936508
Nat Med. 2007 Nov;13(11):1333-40
pubmed: 17982462
Cancer Res. 2008 Jul 1;68(13):5405-13
pubmed: 18593943
J Mol Endocrinol. 2012 Sep 05;49(2):153-63
pubmed: 22872134
J Leukoc Biol. 1999 Jan;65(1):2-5
pubmed: 9886240
J Neural Transm Suppl. 2000;(60):273-6
pubmed: 11205146
Cold Spring Harb Perspect Med. 2017 Oct 3;7(10):
pubmed: 28389514
Eur J Clin Invest. 2007 Feb;37(2):126-33
pubmed: 17217378