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Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, November 2015
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Title
Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines
Published in
Journal of Experimental & Clinical Cancer Research, November 2015
DOI 10.1186/s13046-015-0259-x
Pubmed ID
Authors

Margaretha A. Skowron, Günter Niegisch, Gerhard Fritz, Tanja Arent, Joep G. H. van Roermund, Andrea Romano, Peter Albers, Wolfgang A. Schulz, Michèle J. Hoffmann

Abstract

Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro. Magnetic- and fluorescence-activated- cell sorting were used for separation of CD90(+) and CD90(-) UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs. We observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90(+) cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90(+) cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90(+) cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes. Our findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 20%
Student > Ph. D. Student 3 15%
Student > Doctoral Student 2 10%
Researcher 2 10%
Student > Master 2 10%
Other 3 15%
Unknown 4 20%
Readers by discipline Count As %
Medicine and Dentistry 7 35%
Biochemistry, Genetics and Molecular Biology 2 10%
Agricultural and Biological Sciences 2 10%
Nursing and Health Professions 1 5%
Business, Management and Accounting 1 5%
Other 2 10%
Unknown 5 25%

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 08 December 2015.
All research outputs
#9,990,100
of 12,480,907 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#413
of 768 outputs
Outputs of similar age
#232,447
of 341,589 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#42
of 86 outputs
Altmetric has tracked 12,480,907 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 768 research outputs from this source. They receive a mean Attention Score of 2.4. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,589 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 86 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.