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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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. / Rajpert-De Meyts, E; Poll, S N; Goukasian, I; Jeanneau, C; Herlihy, A S; Bennett, E P; Skakkebaek, N E; Clausen, H; Giwercman, A; Mandel, U.
In: Virchows Archiv, Vol. 451, No. 4, 2007, p. 805-14.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Rajpert-De Meyts, E
AU - Poll, S N
AU - Goukasian, I
AU - Jeanneau, C
AU - Herlihy, A S
AU - Bennett, E P
AU - Skakkebaek, N E
AU - Clausen, H
AU - Giwercman, A
AU - Mandel, U
N1 - Keywords: Antigens, Tumor-Associated, Carbohydrate; Antigens, Viral, Tumor; Cell Differentiation; Cell Transformation, Neoplastic; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; N-Acetylgalactosaminyltransferases; Phenotype; Spermatogenesis; Spermatozoa; Testicular Neoplasms; Testis
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1007/s00428-007-0478-4
DO - 10.1007/s00428-007-0478-4
M3 - Journal article
C2 - 17694322
VL - 451
SP - 805
EP - 814
JO - Virchows Archiv
JF - Virchows Archiv
SN - 0945-6317
IS - 4
ER -
ID: 17654498