Open AccessThe isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets
Author(s) -
PodeShakked Naomi,
Shukrun Rachel,
MarkDanieli Michal,
Tsvetkov Peter,
Bahar Sarit,
PriChen Sara,
Goldstein Ronald S.,
RomGross Eithan,
Mor Yoram,
Fridman Edward,
Meir Karen,
Simon Amos,
Magister Marcus,
Kaminski Naftali,
Goldmacher Victor S.,
HarariSteinberg Orit,
Dekel Benjamin
Publication year - 2013
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201516
Subject(s) - cancer research , cancer stem cell , cancer , transplantation , wilms' tumor , population , cell sorting , cancer cell , pediatric cancer , biology , medicine , pathology , immunology , flow cytometry , environmental health
There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated-NCAM1 expressing-"blastema" phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets.