IngentaConnect Changes in the profile of simple mucin-type O-glycans and polypep...

Authors: Rajpert-De Meyts, E.¹; Poll, S.²; Goukasian, I.²; Jeanneau, C.³; Herlihy, A.²; Bennett, E.³; Skakkebæk, N.²; Clausen, H.³; Giwercman, A.²; Mandel, U.³

Source: Virchows Archiv, Volume 451, Number 4, October 2007 , pp. 805-814(10)

Publisher: Springer

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.

Keywords: Testicular neoplasm; Glycosyltransferases; GalNAc-transferases; Mucin-type O-linked glycosylation; Carcinoma in situ testis

Document Type: Research article

DOI: 10.1007/s00428-007-0478-4

Affiliations: 1: University Department of Growth and Reproduction, Section GR-5064, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark, Email: erm@rh.hosp.dk 2: University Department of Growth and Reproduction, Section GR-5064, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark 3: Departments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen, Nørre Alle 20, 2200, Copenhagen, Denmark

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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