Stem Cell Origin of Testicular Seminoma

作者：Som Avik; Wen Sijin; Tu Shi Ming^*

来源：Clinical Genitourinary Cancer, 2013, 11(4): 489-494.

DOI：10.1016/j.clgc.2013.04.015

• Cancer-initiating cells
• De-differentiation
• Germ cell tumor
• Spermatogonial stem cells
• Stemness

A major question regarding cancer is its cells of origin. The discovery of diverse tumors being derived from a hierarchy of stem cells may pave the way to prove the theory of a stem cell origin of cancers. To our knowledge, we have evidence for the first time in human samples that unique germ cell tumors are linked to particular germline stem cells on the basis of their molecular expression profile. We postulated that distinct malignant subtypes arise from certain stem cells in a stem cell hierarchy. %26lt;br%26gt;Introduction: A major question concerning cancer is its cells of origin. We hypothesized that distinct cancer subtypes arise from unique cancer-initiating cells. By performing a microarray meta-analysis of seminomas and spermatogonial stem cells, we investigated a putative cell of origin for seminoma. Materials and Methods: We obtained published microarray data for 6 human adult germ cell lines, 16 embryonic stem cell lines, 3 normal testicular tissue samples, and 40 seminomas from the Gene Expression Omnibus database. By assessing correlations between various tissue microarrays, we determined the number of transitional events and the distance between seminomas and human spermatogonial stem cells. Results: Our meta-analysis showed that spermatogonial stem cells correlated similarly with seminoma (95% CI of Spearman rho, 0.33-0.44) and with normal somatic testicular tissue cells (95% CI, 0.39-0.40), which suggests parallel paths of cellular origins. Conclusion: Analysis of our results suggests that a unique cancer subtype, namely seminoma, may have originated from an undifferentiated cell with stemness features rather than from a differentiated cell that acquired stemness features.

• 出版日期2013-12