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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

Meyts, E. Rajpert-De; Poll, S. N.; Goukasian, I.; Jeanneau, C.; Herlihy, A. S.; Bennett, E. P.; Skakkebaek, N. E.; Clausen, H.; Giwercman, Aleksander LU and Mandel, U. (2007) In Virchows Archiv: an international journal of pathology 451(4). p.805-814
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 Ga1NAc-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... (More)
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 Ga1NAc-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 Ga1NAc-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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mucin-type O-linked glycosylation, GalNAc-transferases, testicular neoplasm, glycosyltransferases, carcinoma in situ testis
in
Virchows Archiv: an international journal of pathology
volume
451
issue
4
pages
805 - 814
publisher
Springer
external identifiers
  • wos:000249804000008
  • scopus:34848823391
ISSN
1432-2307
DOI
10.1007/s00428-007-0478-4
language
English
LU publication?
yes
id
8984ac55-777d-479d-8f7f-9e70bf5cc2ac (old id 655830)
date added to LUP
2007-12-14 08:57:00
date last changed
2017-05-14 04:20:02
@article{8984ac55-777d-479d-8f7f-9e70bf5cc2ac,
  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 Ga1NAc-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 Ga1NAc-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.},
  author       = {Meyts, E. Rajpert-De and Poll, S. N. and Goukasian, I. and Jeanneau, C. and Herlihy, A. S. and Bennett, E. P. and Skakkebaek, N. E. and Clausen, H. and Giwercman, Aleksander and Mandel, U.},
  issn         = {1432-2307},
  keyword      = {mucin-type O-linked glycosylation,GalNAc-transferases,testicular neoplasm,glycosyltransferases,carcinoma in situ testis},
  language     = {eng},
  number       = {4},
  pages        = {805--814},
  publisher    = {Springer},
  series       = {Virchows Archiv:  an international journal of pathology},
  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},
  url          = {http://dx.doi.org/10.1007/s00428-007-0478-4},
  volume       = {451},
  year         = {2007},
}