Origin of pluripotent germ cell tumours: The role of microenvironment during embryonic development
Origin of pluripotent germ cell tumours: The role of microenvironment during embryonic development
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DOI：
10.1016/j.mce.2008.02.018
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发表时间：
2008-06-25
影响因子：
4.1
通讯作者：
Meyts, Ewa Rajpert-De
中科院分区：
文献类型：
--
作者：
Kristensen, David Mobjerg;Sonne, Si Brask;Meyts, Ewa Rajpert-De
睾丸原位癌（CIS），也称为小管内生殖细胞瘤，是绝大多数睾丸生殖细胞源性肿瘤（TGCTs）产生的癌症干细胞。tgct可以增殖成形态均匀的精原细胞瘤，也可以分化成几乎任何类型的组织并形成畸胎瘤（非精原细胞瘤）。CIS细胞表现出与胎儿生殖细胞（原始生殖细胞或性腺细胞）密切的表型相似性，表明其起源是由于早期生殖细胞发育迟缓或分化受阻。这些肿瘤的多能性最近被解释为它们的表达谱与胚胎干细胞中研究的胚胎内细胞群细胞的表达谱非常相似，具有高表达的与多能性相关的转录因子，如NANOG和OCT3/4，以及在几种组织特异性干细胞中发现的蛋白质，如TFAP2C （AP-2 γ）或KIT。CIS和精原细胞瘤高度表达许多减数分裂前生殖细胞特异性基因，这些基因在发育为非精原细胞瘤的过程中下调，而其他胚胎标志物，如SOX2的表达则上调。胎儿生殖细胞向CIS细胞的初始转化以及CIS细胞向青年侵袭性肿瘤的进展的机制途径和致病因素仍有待阐明。然而，流行病学研究支持的证据表明，分化性腺激素微环境的紊乱可能导致肿瘤和以后生活中的许多其他问题，如生殖器畸形、精子发生减少和性腺功能减退的迹象。2008爱思唯尔爱尔兰有限公司版权所有。
Carcinoma in situ (CIS) testis, known also as intratubular germ cell neoplasia, is the cancer stem cell from which the great majority of testicular germ cell derived tumours (TGCTs) of the testis arise. TGCTs can proliferate into morphologically homogeneous seminomas or can differentiate into virtually any type of tissue and form teratomas (non-seminomas). CIS cells display a close phenotypic similarity to fetal germ cells (primordial germ cells or gonocytes) suggesting an origin due to a developmental delay or arrest of differentiation of early germ cells. The pluripotency of these neoplasms has recently been explained by a close resemblance of their expression profile to that of embryonic inner cell mass cells studied in culture as embryonic stem cells, with high expression of transcription factors associated with pluripotency, such as NANOG and OCT3/4, as well as proteins found in several tissue specific stem cells, such as TFAP2C (AP-2 gamma) or KIT. CIS and seminomas highly express a number of pre-meiotic germ cell specific genes, which are down-regulated during development to non-seminomas, while the expression of other embryonic markers, such as SOX2, is up-regulated. The mechanistic pathways and causative factors remain to be elucidated of both the initial transformation of fetal germ cells into CIS cells and the progression of CIS cells into an invasive tumour in the young adult. However, evidence supported by epidemiological studies indicate that disturbances in the hormonal microenvironment of the differentiating gonads may results in both the neoplasia and a host of other problems later in life, such as genital malformations, decreased spermatogenesis, and signs of hypogonadism. (C) 2008 Elsevier Ireland Ltd. All rights reserved.