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The stem and roots of Wilms' tumours.

Hohenstein P - EMBO Mol Med (2012)

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK. peter.hohenstein@roslin.ed.ac.uk

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See related article in EMBO Molecular Medicine http://dx.doi.org/10.1002/emmm.201201516 The cancer stem cell (CSC) concept goes back a long way... Wilms' tumours (WT) have fascinated pathologists and developmental biologists alike for a long time... Found in the kidneys of children usually before the age of five, they show structures normally found in developing, embryonic kidneys... NCAM cells show enrichment in early renal progenitor markers, stem cell factors and known poor prognosis factors... Moreover, Xn samples from NCAM cells can recapitulate the complex histology found in WT, including NCAM descendent cells... Not only does this indirectly further confirm the CSC state of the NCAM cells, it provides a potential therapeutic approach based on these findings... Despite the greatly improved survival of children with WT, patients that do relapse respond much worse to subsequent therapy and increasingly later onset malignancies are found in former WT patients decades after treatment, likely to be secondary effects of the original therapy... The demonstration of successfully targeted NCAM WT CSC has therefore important clinical implications... The identification of NCAM WT CSC provides clues about, but does not identify the cell of origin of these tumours... NCAM is expressed in the cap-mesenchyme cells that give rise to the complete nephron, but not much is known about the NCAM cells found there... All WT CSC described by Pode-Shakked et al were derived from WT1-wild type tumours... More analyses will be needed to determine if the WT1-mutant tumours also harbour NCAMALDH1 CSC... Furthermore, the genetic aberrations that drive the WT1-wild type tumours need to be clarified before their influence on the NCAMALDH1 CSC can be taken into account... The identification of the NCAMALDH1 WT CSC is an essential step towards a further increase in (long-term) survival of the patients. »More important for the patients, at least in the shorter term, is that the study by Pode-Shakked et al demonstrates a new approach for the treatment of the largest and clinically most difficult class of Wilms' tumours. «

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The use of small Wilms' tumour fragments in xenograft experiments greatly improves the efficiency with which these grafts are formedOnce a xenograft line is established, the efficiency of propagation further increases per passage and through FACS sorting for NCAM+ALDH1+ cells.
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fig01: The use of small Wilms' tumour fragments in xenograft experiments greatly improves the efficiency with which these grafts are formedOnce a xenograft line is established, the efficiency of propagation further increases per passage and through FACS sorting for NCAM+ALDH1+ cells.

Mentions: Through an optimized Xn protocol, Pode-Shakked et al. now identify NCAM+ALDH1+ cells as WT CSC (Fig 1). Whereas >10,000 unsorted WT cells need to be injected into immune-compromised mice for Xn propagation, only 500 NCAM+ or 200 NCAM+ALDH1+ are required for this. NCAM+ cells show enrichment in early renal progenitor markers, stem cell factors and known poor prognosis factors. Moreover, Xn samples from NCAM+ cells can recapitulate the complex histology found in WT, including NCAM− descendent cells. This capability is even maintained after serial transplantations confirming the self-renewal capacity of the cells. Together with other lines of evidence provided, this clearly identifies the NCAM+ALDH1+ cells as WT CSC. But most importantly, the authors show that targeting the NCAM+ population with cytotoxic drug-conjugated anti-NCAM antibodies effectively eradicates WT Xn samples. Not only does this indirectly further confirm the CSC state of the NCAM+ cells, it provides a potential therapeutic approach based on these findings. Despite the greatly improved survival of children with WT, patients that do relapse respond much worse to subsequent therapy and increasingly later onset malignancies are found in former WT patients decades after treatment, likely to be secondary effects of the original therapy. The demonstration of successfully targeted NCAM+ WT CSC has therefore important clinical implications.


The stem and roots of Wilms' tumours.

Hohenstein P - EMBO Mol Med (2012)

The use of small Wilms' tumour fragments in xenograft experiments greatly improves the efficiency with which these grafts are formedOnce a xenograft line is established, the efficiency of propagation further increases per passage and through FACS sorting for NCAM+ALDH1+ cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569648&req=5

fig01: The use of small Wilms' tumour fragments in xenograft experiments greatly improves the efficiency with which these grafts are formedOnce a xenograft line is established, the efficiency of propagation further increases per passage and through FACS sorting for NCAM+ALDH1+ cells.
Mentions: Through an optimized Xn protocol, Pode-Shakked et al. now identify NCAM+ALDH1+ cells as WT CSC (Fig 1). Whereas >10,000 unsorted WT cells need to be injected into immune-compromised mice for Xn propagation, only 500 NCAM+ or 200 NCAM+ALDH1+ are required for this. NCAM+ cells show enrichment in early renal progenitor markers, stem cell factors and known poor prognosis factors. Moreover, Xn samples from NCAM+ cells can recapitulate the complex histology found in WT, including NCAM− descendent cells. This capability is even maintained after serial transplantations confirming the self-renewal capacity of the cells. Together with other lines of evidence provided, this clearly identifies the NCAM+ALDH1+ cells as WT CSC. But most importantly, the authors show that targeting the NCAM+ population with cytotoxic drug-conjugated anti-NCAM antibodies effectively eradicates WT Xn samples. Not only does this indirectly further confirm the CSC state of the NCAM+ cells, it provides a potential therapeutic approach based on these findings. Despite the greatly improved survival of children with WT, patients that do relapse respond much worse to subsequent therapy and increasingly later onset malignancies are found in former WT patients decades after treatment, likely to be secondary effects of the original therapy. The demonstration of successfully targeted NCAM+ WT CSC has therefore important clinical implications.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK. peter.hohenstein@roslin.ed.ac.uk

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

See related article in EMBO Molecular Medicine http://dx.doi.org/10.1002/emmm.201201516 The cancer stem cell (CSC) concept goes back a long way... Wilms' tumours (WT) have fascinated pathologists and developmental biologists alike for a long time... Found in the kidneys of children usually before the age of five, they show structures normally found in developing, embryonic kidneys... NCAM cells show enrichment in early renal progenitor markers, stem cell factors and known poor prognosis factors... Moreover, Xn samples from NCAM cells can recapitulate the complex histology found in WT, including NCAM descendent cells... Not only does this indirectly further confirm the CSC state of the NCAM cells, it provides a potential therapeutic approach based on these findings... Despite the greatly improved survival of children with WT, patients that do relapse respond much worse to subsequent therapy and increasingly later onset malignancies are found in former WT patients decades after treatment, likely to be secondary effects of the original therapy... The demonstration of successfully targeted NCAM WT CSC has therefore important clinical implications... The identification of NCAM WT CSC provides clues about, but does not identify the cell of origin of these tumours... NCAM is expressed in the cap-mesenchyme cells that give rise to the complete nephron, but not much is known about the NCAM cells found there... All WT CSC described by Pode-Shakked et al were derived from WT1-wild type tumours... More analyses will be needed to determine if the WT1-mutant tumours also harbour NCAMALDH1 CSC... Furthermore, the genetic aberrations that drive the WT1-wild type tumours need to be clarified before their influence on the NCAMALDH1 CSC can be taken into account... The identification of the NCAMALDH1 WT CSC is an essential step towards a further increase in (long-term) survival of the patients. »More important for the patients, at least in the shorter term, is that the study by Pode-Shakked et al demonstrates a new approach for the treatment of the largest and clinically most difficult class of Wilms' tumours. «

Show MeSH
Related in: MedlinePlus