Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte
Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte
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DOI：
10.1158/0008-5472.can-08-4554
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发表时间：
2009-06-15
期刊：
影响因子：
11.2
通讯作者：
Leffers, Henrik
中科院分区：
文献类型：
--
作者：
Sonne, Si Brask;Almstrup, Kristian;Leffers, Henrik
年轻成年男性的睾丸生殖细胞癌源自称为睾丸原位癌 (CIS) 的前体病变。 CIS 细胞被认为源自原始生殖细胞或生殖母细胞。然而，缺乏对 CIS 细胞纯化样品的直接研究。为了克服这个问题，我们对 CIS 细胞进行了激光显微切割。获得高度富集的细胞群并进行基因表达分析。将 CIS 细胞的表达谱与显微解剖的生殖母细胞、卵原细胞和有或没有基因组畸变的培养胚胎干细胞进行比较。每种组织类型的三个样本用于分析。这些发育上非常相关的细胞类型的独特表达模式表明，CIS 细胞与生殖母细胞非常相似，因为只有五个基因区分这两种细胞类型。我们没有发现 CIS 源自减数分裂细胞的迹象，并且与生殖母细胞相比，与胚胎干细胞的相似性不大。因此，我们提供了新的证据表明 CIS 细胞的分子表型与生殖细胞相似。我们的数据符合 CIS 细胞可能是出生后睾丸中存活的生殖母细胞的观点。推测胎儿睾丸中体细胞发育紊乱可能在允许未分化细胞在出生后睾丸中存活方面发挥作用。 CIS 进一步发展为侵袭性生殖细胞肿瘤可能取决于青春期后体细胞生态位的信号，包括来自 Leydig 和 Sertoli 细胞的激素和生长因子。 [癌症研究 2009;69(12):5241-50]
Testicular germ cell cancers in young adult men derive from a precursor lesion called carcinoma in situ (CIS) of the testis. CIS cells were suggested to arise from primordial germ cells or gonocytes. However, direct studies on purified samples of CIS cells are lacking. To overcome this problem, we performed laser microdissection of CIS cells. Highly enriched cell populations were obtained and subjected to gene expression analysis. The expression profile of CIS cells was compared with microdissected gonocytes, oogonia, and cultured embryonic stem cells with and without genomic aberrations. Three samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from a meiotic cell, and the similarity to embryonic stem cells was modest compared with gonocytes. Thus, we provide new evidence that the molecular phenotype of CIS cells is similar to that of gonocytes. Our data are in line with the idea that CIS cells may be gonocytes that survived in the postnatal testis. speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including hormones and growth factors from Leydig and Sertoli cells. [Cancer Res 2009;69(12):5241-50]