Abstract
Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.
| Original language | English |
|---|---|
| Pages (from-to) | 1331-1343 |
| Number of pages | 13 |
| Journal | Brain |
| Volume | 134 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2011 |
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Keywords
- brain tumour
- cancer stem cells
- glioblastoma
- label-retaining cells
- tumour-initiating cells
ASJC Scopus subject areas
- Clinical Neurology
Cite this
Evidence for label-retaining tumour-initiating cells in human glioblastoma. / Deleyrolle, Loic P.; Harding, Angus; Cato, Kathleen; Siebzehnrubl, Florian A.; Rahman, Maryam; Azari, Hassan; Olson, Sarah; Gabrielli, Brian; Osborne, Geoffrey; Vescovi, Angelo; Reynolds, Brent A.
In: Brain, Vol. 134, No. 5, 05.2011, p. 1331-1343.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence for label-retaining tumour-initiating cells in human glioblastoma
AU - Deleyrolle, Loic P.
AU - Harding, Angus
AU - Cato, Kathleen
AU - Siebzehnrubl, Florian A.
AU - Rahman, Maryam
AU - Azari, Hassan
AU - Olson, Sarah
AU - Gabrielli, Brian
AU - Osborne, Geoffrey
AU - Vescovi, Angelo
AU - Reynolds, Brent A.
PY - 2011/5
Y1 - 2011/5
N2 - Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.
AB - Individual tumour cells display diverse functional behaviours in terms of proliferation rate, cell-cell interactions, metastatic potential and sensitivity to therapy. Moreover, sequencing studies have demonstrated surprising levels of genetic diversity between individual patient tumours of the same type. Tumour heterogeneity presents a significant therapeutic challenge as diverse cell types within a tumour can respond differently to therapies, and inter-patient heterogeneity may prevent the development of general treatments for cancer. One strategy that may help overcome tumour heterogeneity is the identification of tumour sub-populations that drive specific disease pathologies for the development of therapies targeting these clinically relevant sub-populations. Here, we have identified a dye-retaining brain tumour population that displays all the hallmarks of a tumour-initiating sub-population. Using a limiting dilution transplantation assay in immunocompromised mice, label-retaining brain tumour cells display elevated tumour-initiation properties relative to the bulk population. Importantly, tumours generated from these label-retaining cells exhibit all the pathological features of the primary disease. Together, these findings confirm dye-retaining brain tumour cells exhibit tumour-initiation ability and are therefore viable targets for the development of therapeutics targeting this sub-population.
KW - brain tumour
KW - cancer stem cells
KW - glioblastoma
KW - label-retaining cells
KW - tumour-initiating cells
UR - http://www.scopus.com/inward/record.url?scp=79957472391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957472391&partnerID=8YFLogxK
U2 - 10.1093/brain/awr081
DO - 10.1093/brain/awr081
M3 - Article
C2 - 21515906
AN - SCOPUS:79957472391
VL - 134
SP - 1331
EP - 1343
JO - Brain
JF - Brain
SN - 0006-8950
IS - 5
ER -