Wilms' tumor blastemal stem cells dedifferentiate to propagate the tumor bulk

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalStem Cell Reports
Volume3
Issue number1
DOIs
StatePublished - 8 Jul 2014

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