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人类发育中的睾丸、原位睾丸癌和生殖细胞肿瘤中M2A(D2-40)抗原与gp36(Aggrus、T1A-2、血小板反应蛋白1)的一致性

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

作者信息

Sonne Si Brask, Herlihy Amy S, Hoei-Hansen Christina E, Nielsen John E, Almstrup Kristian, Skakkebaek Niels E, Marks Alexander, Leffers Henrik, Rajpert-De Meyts Ewa

机构信息

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

出版信息

Virchows Arch. 2006 Aug;449(2):200-6. doi: 10.1007/s00428-006-0223-4. Epub 2006 May 31.

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.

摘要

年轻成年人的睾丸生殖细胞肿瘤源自一种侵袭前的小管内病变,即原位癌(CIS)。在最近一项使用cDNA微阵列进行的全基因组基因表达筛选中,我们发现与正常成年睾丸相比,PDPN在CIS中过度表达。PDPN编码血小板内皮细胞黏附分子(Aggrus、人gp36、T1A-2),这是一种在淋巴管内皮和各种实体瘤中表达的跨膜糖蛋白。为了研究PDPN在睾丸肿瘤以及睾丸发育过程中的潜在作用,我们调查了其在人类睾丸发育过程中以及一系列睾丸CIS、性腺母细胞瘤和明显的生殖细胞肿瘤中的表达模式。我们通过RT-PCR以及使用gp36抗体的免疫组织化学方法证实,PDPN mRNA和蛋白质产物在患有生殖细胞肿瘤的睾丸中表达,但在正常成年睾丸中不表达。我们还在早期胎儿生殖母细胞和未成熟支持细胞中发现了gp36表达,这与M2A抗原(一种先前确定的CIS和精原细胞瘤标志物)的表达模式相似。这强化了我们之前的提议,即M2A(D2-40)抗原与gp36(血小板内皮细胞黏附分子、Aggrus、T1A-2)相同。我们的研究结果还表明,血小板内皮细胞黏附分子在睾丸发育过程中具有功能,很可能在减数分裂前生殖细胞和未成熟支持细胞之间的细胞间相互作用层面发挥作用。

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