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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

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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.

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Acknowledgement

The authors thank Professor P. W. Andrews for a generous gift of NT/D1 cell line and TRA-1-60 antibody, Dr N. Jørgensen for fetal tissue specimens, the pathologists at several pathology departments in the Greater Copenhagen area for assistance in obtaining tissue specimens and L. Andersen, H. Kistrup and T. Adelfest for skilful technical assistance. This work was supported by grants from the Danish Cancer Society, the Svend Andersen Foundation, the Vissing Foundation, the Kirsten and Freddy Johansen Foundation, the Willumsen Foundation and the Danish Medical Research Council.

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Authors and Affiliations

  1. University Department of Growth and Reproduction, Section GR-5064, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    E. Rajpert-De Meyts, S. N. Poll, I. Goukasian, A. S. Herlihy, N. E. Skakkebæk & A. Giwercman

  2. Departments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen, Nørre Alle 20, 2200, Copenhagen, Denmark

    C. Jeanneau, E. P. Bennett, H. Clausen & U. Mandel

  3. Fertility Centre and Department of Urology, Malmö University Hospital, Lund University, Malmö, Sweden

    A. Giwercman

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  1. E. Rajpert-De Meyts
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  3. I. Goukasian
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  6. E. P. Bennett
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  9. A. Giwercman
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Correspondence to E. Rajpert-De Meyts.

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E. Rajpert-De Meyts and S. N. Poll contributed equally to this study.

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Rajpert-De Meyts, E., Poll, S.N., Goukasian, I. et al. 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. Virchows Arch 451, 805–814 (2007). https://doi.org/10.1007/s00428-007-0478-4

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