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Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours

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Abstract

Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus, human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours. To examine a potential role for PDPN in testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of testicular CIS, gonadoblastoma and overt germ-cell tumours. We established by RT-PCR and by immunohistochemistry with a gp36 antibody that PDPN mRNA and the protein product were expressed in testes with germ-cell neoplasms but not in the normal adult testis. We also found gp36 expression in early foetal gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has a function in developing testis, most likely at the level of cell–cell interactions among pre-meiotic germ cells and immature Sertoli cells.

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Acknowledgements

The authors wish to thank L. Andersen and H. Kistrup for the skilful technical assistance, Drs. N. Jørgensen and N. Græm for providing some foetal and prepubertal testis samples, and Dr. P. Andrews for kindly providing TRA-1-60 antibody. This work was supported by grants from the Danish Cancer Society, Svend Andersen’s Foundation, the Danish Medical Research Council, the Kirsten and Freddy Johansen’s Foundation, Willumsen’s Foundation and the Vissing Foundation. The experiments presented in the present manuscript comply with the Danish law.

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Correspondence to Si Brask Sonne.

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Sonne, S.B., Herlihy, A.S., Hoei-Hansen, C.E. et al. Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours. Virchows Arch 449, 200–206 (2006). https://doi.org/10.1007/s00428-006-0223-4

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