title: Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation.
abstract: Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin-type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1-4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated nonseminoma, i.e. embryonal carcinoma, whereas teratomas expressed them all to some extent but in a disorganized manner. We concluded that simple mucin-type O-glycans and their transferases are developmentally regulated in the human testis, with profound changes associated with neoplasia. The restricted O-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell differentiation.
authors: University Department of Growth and Reproduction, Section GR-5064, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. erm@rh.hosp.dk
authors: E
authors: E
authors: Rajpert-De Meyts
authors: S N
authors: SN
authors: Poll
authors: I
authors: I
authors: Goukasian
authors: C
authors: C
authors: Jeanneau
authors: A S
authors: AS
authors: Herlihy
authors: E P
authors: EP
authors: Bennett
authors: N E
authors: NE
authors: Skakkebaek
authors: H
authors: H
authors: Clausen
authors: A
authors: A
authors: Giwercman
authors: U
authors: U
authors: Mandel
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000235:genetics / Q000378:metabolism*; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000473:pathology; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000957:Antigens, Viral, Tumor; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C040286:Tn antigen; C055491:sialosyl-Tn antigen
references: Hybridoma. 1984 Winter;3(4):347-61
references: 6396197
references: Dev Biol. 1984 Jun;103(2):285-93
references: 6144603
references: J Biol Chem. 1999 Sep 3;274(36):25362-70
references: 10464263
references: Br J Cancer. 1996 Jul;74(1):133-40
references: 8679447
references: Int J Cancer. 1996 Jun 11;66(6):806-16
references: 8647654
references: Virchows Arch. 2006 Aug;449(2):200-6
references: 16736189
references: J Biol Chem. 2002 Jun 21;277(25):22623-38
references: 11925450
references: Cell. 2003 Aug 22;114(4):405-17
references: 12941270
references: Virchows Arch. 1995;426(4):369-74
references: 7599789
references: J Clin Endocrinol Metab. 2005 Apr;90(4):2420-3
references: 15687324
references: J Biol Chem. 1998 Nov 13;273(46):30472-81
references: 9804815
references: Nat Genet. 2004 Jun;36(6):579-81
references: 15133511
references: Lab Invest. 1995 Feb;72(2):223-31
references: 7531795
references: J Biol Chem. 2005 Jul 22;280(29):27310-8
references: 15917254
references: Nat Rev Cancer. 2005 Jul;5(7):526-42
references: 16069816
references: APMIS. 2003 Jan;111(1):267-78; discussion 278-9
references: 12752272
references: Lancet. 1972 Sep 9;2(7776):516-7
references: 4115573
references: Glycobiology. 1996 Sep;6(6):635-46
references: 8922959
references: Int J Androl. 1987 Feb;10(1):19-28
references: 3034791
references: Glycoconj J. 2001 Nov-Dec;18(11-12):883-93
references: 12820722
references: Glycobiology. 1998 Jun;8(6):547-55
references: 9592121
references: Cancer Res. 2003 May 1;63(9):2244-50
references: 12727846
references: J Clin Pathol. 2006 Apr;59(4):440-2
references: 16567474
references: APMIS. 1991 May;99(5):391-7
references: 1710473
references: J Biol Chem. 1995 Nov 3;270(44):26025-8
references: 7592795
references: APMIS. 1998 Jan;106(1):198-204; discussion 204-6
references: 9524579
references: Proc Natl Acad Sci U S A. 1986 Jul;83(14):5291-5
references: 3523489
references: Hum Reprod Update. 1999 Jul-Aug;5(4):314-29
references: 10465523
references: Am J Dermatopathol. 2005 Jun;27(3):211-5
references: 15900124
references: Glycobiology. 1999 Jan;9(1):43-52
references: 9884405
references: Nat Rev Drug Discov. 2005 Jun;4(6):477-88
references: 15931257
references: EMBO Rep. 2006 Jun;7(6):599-604
references: 16741504
references: Hum Reprod Update. 2006 May-Jun;12(3):303-23
references: 16540528
references: Int J Cancer. 1994 Jul 1;58(1):108-15
references: 8014006
references: J Invest Dermatol. 1991 Oct;97(4):713-21
references: 1940443
references: Histopathology. 2005 Jul;47(1):48-56
references: 15982323
references: Acta Pathol Microbiol Immunol Scand A. 1984 Sep;92(5):323-9
references: 6209917
references: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6193-7
references: 9600940
references: Cancer Res. 2004 Jul 15;64(14):4736-43
references: 15256440
references: Hum Reprod. 2002 Aug;17(8):2199-208
references: 12151459
references: Science. 1984 Jun 15;224(4654):1198-206
references: 6729450
references: Am J Pathol. 2005 Mar;166(3):913-21
references: 15743802
references: Cancer. 2005 Nov 15;104(10 ):2092-8
references: 16206293
references: J Biol Chem. 2004 Sep 10;279(37):38838-43
references: 15231832