Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men.
Animals
Antigens, Neoplasm
/ analysis
Blood-Testis Barrier
Extracellular Fluid
/ chemistry
Humans
Immunotherapy
Infertility, Male
/ metabolism
Male
Mice
Neoplasms
/ therapy
Proteins
/ analysis
Proteome
Seminiferous Tubules
/ metabolism
Sertoli Cells
/ physiology
Spermatogenesis
Spermatozoa
/ chemistry
Testis
/ metabolism
biomarker
cancer-testis antigen
interstitial fluid
sperm
testis
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
09
11
2020
revised:
21
12
2020
accepted:
11
01
2021
entrez:
10
2
2021
pubmed:
11
2
2021
medline:
27
7
2021
Statut:
ppublish
Résumé
Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.
Identifiants
pubmed: 33565176
doi: 10.1096/fj.202002484R
pmc: PMC7898903
doi:
Substances chimiques
Antigens, Neoplasm
0
Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21397Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J015105/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
Références
Oncotarget. 2018 Nov 13;9(89):35997-36011
pubmed: 30542513
Oncogene. 2018 Oct;37(42):5694-5700
pubmed: 29907769
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
J Androl. 2011 Nov-Dec;32(6):625-40
pubmed: 21764900
Med Mol Morphol. 2012 Dec;45(4):185-9
pubmed: 23224596
Mol Hum Reprod. 1999 Jul;5(7):627-35
pubmed: 10381817
Biol Reprod. 2003 May;68(5):1525-37
pubmed: 12606493
Int J Clin Exp Pathol. 2013 Nov 15;6(12):2835-45
pubmed: 24294369
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20422-7
pubmed: 19088187
Asian J Androl. 2013 Jan;15(1):35-9
pubmed: 23241638
Semin Cell Dev Biol. 2016 Nov;59:166-173
pubmed: 27353840
Proteomics. 2016 Sep;16(17):2391-402
pubmed: 27324652
Nat Rev Cancer. 2005 Aug;5(8):615-25
pubmed: 16034368
Am J Anat. 1974 May;140(1):1-25
pubmed: 4132933
J Exp Med. 2017 Oct 2;214(10):2829-2841
pubmed: 28784628
J Leukoc Biol. 2018 Oct;104(4):757-766
pubmed: 30265772
Biol Reprod. 2013 Feb 21;88(2):41
pubmed: 23303679
Mol Hum Reprod. 2014 Jun;20(6):476-88
pubmed: 24598113
Semin Cancer Biol. 2018 Dec;53:75-89
pubmed: 30171980
Proc Natl Acad Sci U S A. 2011 May 3;108(18):7511-6
pubmed: 21502500
Oncotarget. 2015 Feb 20;6(5):2812-26
pubmed: 25739119
Int J Androl. 1992 Jun;15(3):201-10
pubmed: 1399083
Cancer Immunol Immunother. 2020 Mar;69(3):449-463
pubmed: 31932876
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7712-7
pubmed: 16682651
J Immunol. 1987 Feb 1;138(3):752-9
pubmed: 3492532
FASEB J. 2018 Mar;32(3):1653-1664
pubmed: 29183964
Mol Cell Endocrinol. 2011 Mar 15;335(1):60-8
pubmed: 20363290
Annu Rev Pharmacol Toxicol. 2014;54:251-72
pubmed: 24160706
Oncoimmunology. 2016 Feb 9;5(2):e1078965
pubmed: 27057472
BMC Genomics. 2017 Dec 15;18(1):972
pubmed: 29246116
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Oncol Rep. 2012 Nov;28(5):1792-8
pubmed: 22941507
Eur Urol. 2012 Oct;62(4):713-9
pubmed: 22521095
J Reprod Immunol. 2013 Nov;100(1):66-75
pubmed: 24080233
Andrology. 2015 Nov;3(6):1035-49
pubmed: 26446427
J Reprod Immunol. 2002 Oct-Nov;57(1-2):19-34
pubmed: 12385831
Anat Rec. 1977 Mar;187(3):347-66
pubmed: 851237
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
FASEB J. 2021 Mar;35(3):e21397
pubmed: 33565176
Dev Biol. 2002 Jun 15;246(2):480-94
pubmed: 12051831
Mol Reprod Dev. 2014 Oct;81(10):896-907
pubmed: 25158006
Int J Androl. 2007 Feb;30(1):21-7
pubmed: 17328721
Am J Reprod Immunol. 1999 Nov;42(5):321-6
pubmed: 10584988
Oncotarget. 2015 Jun 30;6(18):15772-87
pubmed: 26158218
Cell Rep. 2015 Aug 18;12(7):1107-19
pubmed: 26257171
J Proteome Res. 2017 Nov 3;16(11):4060-4072
pubmed: 28948796
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8346-51
pubmed: 17483452
Immunol Rev. 2006 Oct;213:66-81
pubmed: 16972897
Clin Exp Immunol. 1975 Apr;20(1):93-104
pubmed: 1106922
Proteomics. 2005 Aug;5(13):3531-6
pubmed: 16041672
Semin Cell Dev Biol. 2014 Jun;30:36-44
pubmed: 24603046
J Clin Invest. 2017 Mar 1;127(3):1046-1060
pubmed: 28218625
Immunol Rev. 2006 Aug;212:170-84
pubmed: 16903914
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Spermatogenesis. 2014 Mar 31;4:e28218
pubmed: 25105055
Endocrinology. 1984 Nov;115(5):1925-32
pubmed: 6541571
Cell Tissue Res. 1985;240(2):303-9
pubmed: 3995554
Development. 2014 May;141(10):2139-49
pubmed: 24803659
Nucleic Acids Res. 2014 Jan;42(Database issue):D959-65
pubmed: 24304897
Mol Cell Endocrinol. 2017 Apr 15;445:65-73
pubmed: 27743991
J Biol Chem. 2011 Feb 18;286(7):5639-46
pubmed: 21131354
Nucleic Acids Res. 2009 Jan;37(Database issue):D816-9
pubmed: 18838390
Nat Rev Cancer. 2019 Mar;19(3):151-161
pubmed: 30723290
Biol Reprod. 2015 May;92(5):129
pubmed: 25761597
Hum Reprod. 2018 Nov 1;33(11):1963-1974
pubmed: 30247578
Front Immunol. 2012 Jun 11;3:152
pubmed: 22701457
Crit Rev Oncol Hematol. 2018 Dec;132:17-26
pubmed: 30447924
Br J Urol. 1997 Nov;80(5):691-7
pubmed: 9393288
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
Front Biosci (Landmark Ed). 2011 Jan 01;16(4):1315-30
pubmed: 21196234
Cell Immunol. 2018 Aug;330:120-125
pubmed: 29650243
Mol Cell Biol. 2007 Oct;27(19):6794-805
pubmed: 17664285
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Mol Cell Proteomics. 2006 Jan;5(1):144-56
pubmed: 16219938
PLoS One. 2014 Aug 21;9(8):e105687
pubmed: 25144714
Cancer Treat Rev. 2018 Jun;67:54-62
pubmed: 29763778
J Transl Med. 2009 Jul 15;7:61
pubmed: 19604394
Gamete Res. 1987 May;17(1):43-56
pubmed: 2906900
Lung Cancer. 2018 Nov;125:157-163
pubmed: 30429015
Cancer Sci. 2009 Nov;100(11):2014-21
pubmed: 19719775
Clin Cancer Res. 2004 Oct 1;10(19):6544-50
pubmed: 15475442
Andrologia. 2017 Dec;49(10):
pubmed: 28261828