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Side Population in Human Non-Muscle Invasive Bladder Cancer Enriches for Cancer Stem Cells That Are Maintained by MAPK Signalling

Overview of attention for article published in PLOS ONE, November 2012
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Title
Side Population in Human Non-Muscle Invasive Bladder Cancer Enriches for Cancer Stem Cells That Are Maintained by MAPK Signalling
Published in
PLOS ONE, November 2012
DOI 10.1371/journal.pone.0050690
Pubmed ID
Authors

Anastasia C. Hepburn, Rajan Veeratterapillay, Stuart C. Williamson, Amira El-Sherif, Neha Sahay, Huw D. Thomas, Alejandra Mantilla, Robert S. Pickard, Craig N. Robson, Rakesh Heer

Abstract

Side population (SP) and ABC transporter expression enrich for stem cells in numerous tissues. We explored if this phenotype characterised human bladder cancer stem cells (CSCs) and attempted to identify regulatory mechanisms. Focusing on non-muscle invasive bladder cancer (NMIBC), multiple human cell lines were used to characterise SP and ABC transporter expression. In vitro and in vivo phenotypic and functional assessments of CSC behaviour were undertaken. Expression of putative CSC marker ABCG2 was assessed in clinical NMIBC samples (n = 148), and a role for MAPK signalling, a central mechanism of bladder tumourigenesis, was investigated. Results showed that the ABCG2 transporter was predominantly expressed and was up-regulated in the SP fraction by 3-fold (ABCG2(hi)) relative to the non-SP (NSP) fraction (ABCG2(low)). ABCG2(hi) SP cells displayed enrichment of stem cell markers (Nanog, Notch1 and SOX2) and a three-fold increase in colony forming efficiency (CFE) in comparison to ABCG2(low) NSP cells. In vivo, ABCG2(hi) SP cells enriched for tumour growth compared with ABCG2(low) NSP cells, consistent with CSCs. pERK was constitutively active in ABCG2(hi) SP cells and MEK inhibition also inhibited the ABCG2(hi) SP phenotype and significantly suppressed CFE. Furthermore, on examining clinical NMIBC samples, ABCG2 expression correlated with increased recurrence and decreased progression free survival. Additionally, pERK expression also correlated with decreased progression free survival, whilst a positive correlation was further demonstrated between ABCG2 and pERK expression. In conclusion, we confirm ABCG2(hi) SP enriches for CSCs in human NMIBC and MAPK/ERK pathway is a suitable therapeutic target.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 2 8%
Unknown 22 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 25%
Student > Bachelor 3 13%
Student > Master 3 13%
Student > Postgraduate 2 8%
Professor 1 4%
Other 2 8%
Unknown 7 29%
Readers by discipline Count As %
Medicine and Dentistry 7 29%
Agricultural and Biological Sciences 6 25%
Biochemistry, Genetics and Molecular Biology 2 8%
Neuroscience 1 4%
Engineering 1 4%
Other 0 0%
Unknown 7 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 December 2012.
All research outputs
#20,174,175
of 22,687,320 outputs
Outputs from PLOS ONE
#172,807
of 193,653 outputs
Outputs of similar age
#245,324
of 276,634 outputs
Outputs of similar age from PLOS ONE
#3,904
of 4,722 outputs
Altmetric has tracked 22,687,320 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,653 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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