Details

Autor(en) / Beteiligte

• Shukrun, Rachel
• Pode-Shakked, Naomi
• Pleniceanu, Oren
• Omer, Dorit
• Vax, Einav
• Peer, Eyal
• Pri-Chen, Sara
• Jacob, Jasmine
• Hu, Qianghua
• Harari-Steinberg, Orit
• Huff, Vicki
• Dekel, Benjamin

Titel

Wilms’ Tumor Blastemal Stem Cells Dedifferentiate to Propagate the Tumor Bulk

Ist Teil von

• Stem cell reports, 2014-07, Vol.3 (1), p.24-33

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• An open question remains in cancer stem cell (CSC) biology whether CSCs are by definition at the top of the differentiation hierarchy of the tumor. Wilms’ tumor (WT), composed of blastema and differentiated renal elements resembling the nephrogenic zone of the developing kidney, is a valuable model for studying this question because early kidney differentiation is well characterized. WT neural cell adhesion molecule 1-positive (NCAM1+) aldehyde dehydrogenase 1-positive (ALDH1+) CSCs have been recently isolated and shown to harbor early renal progenitor traits. Herein, by generating pure blastema WT xenografts, composed solely of cells expressing the renal developmental markers SIX2 and NCAM1, we surprisingly show that sorted ALDH1+ WT CSCs do not correspond to earliest renal stem cells. Rather, gene expression and proteomic comparative analyses disclose a cell type skewed more toward epithelial differentiation than the bulk of the blastema. Thus, WT CSCs are likely to dedifferentiate to propagate WT blastema. [Display omitted] •The Wilms’ tumor (WT) blastema can be exclusively propagated in mice•Gene and protein analyses place the WT CSC at a specific developmental stage•WT CSCs do not correspond to the earliest renal stem cells•WT CSCs are likely to dedifferentiate to propagate WT blastema The developmental status of cancer stem cells (CSCs) remains obscure. Wilms’ tumors (WT) are composed of blastema and differentiated renal elements. Herein, by generating pure blastema WT xenografts, Shukrun et al. surprisingly show that sorted NCAM+ALDH1+ WT CSCs do not correspond to the earliest renal stem cells. Rather, the authors show that they are skewed toward epithelial differentiation compared to the blastema bulk. Thus, WT CSCs are likely to dedifferentiate to propagate WT blastema.