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Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling

Overview of attention for article published in Stem Cell Research & Therapy, February 2015
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Title
Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling
Published in
Stem Cell Research & Therapy, February 2015
DOI 10.1186/s13287-015-0002-8
Pubmed ID
Authors

Vijayabaskar Pandian, Satishkumar Ramraj, Faizan H Khan, Tasfia Azim, Natarajan Aravindan

Abstract

High-risk neuroblastoma (HR-NB) presenting with hematogenous metastasis is one of the most difficult cancers to cure. Patient survival is poor. Aggressive tumors contain populations of rapidly proliferating clonogens that exhibit stem cell properties, cancer stem cells (CSCs). Conceptually, CSCs that evade intensive multimodal therapy dictate tumor progression, relapse/recurrence, and poor clinical outcomes. Herein, we investigated the plasticity and stem-cell related molecular response of aggressive metastatic neuroblastoma cells that fit the CSC model. Well-characterized clones of metastatic site-derived aggressive cells (MSDACs) from a manifold of metastatic tumors of clinically translatable HR-NB were characterized for their CSC fit by examining epithelial-to-mesenchymal transition (EMT) (E-cadherin, N-Cadherin), survival (NFκB P65, p50, IκB and pIκB) and drug resistance (ABCG2) by immunoblotting; pluripotency maintenance (Nanog, SOX2) by immunofluorescence; and EMT and stemness related transcription of 93 genes by QPCR profiling. Plasticity of MSDACs under sequential alternation of culture conditions with serum and serum-free stem-cell conditions was assessed by clonal expansion (BrdU incorporation), tumorosphere formation (anchorage independent growth), EMT and stemness related transcriptome (QPCR profiling) and validated with MYC, SOX2, EGFR, NOTCH1 and CXCL2 immunoblotting. HR-NB MSDACs maintained in alternated culture conditions, serum-free stem cell medium to growth medium with serum and vice versa identified its flexible revocable plasticity characteristics. We observed signatures of stem cell-related molecular responses consistent with phenotypic conversions. Successive reintroduction to the favorable niche not only regained identical EMT, self-renewal capacity, pluripotency maintenance, and other stem cell-related signaling events, but also instigated additional events depicting aggressive adaptive plasticity. Together, these results demonstrated the flexible plasticity of HR-NB MSDACs that typically fit the CSC model, and further identified the intrinsic adaptiveness of the successive phenotype switching that clarifies the heterogeneity of HR-NB. Moreover, the continuous ongoing acquisition of stem cell-related molecular rearrangements may hold the key to the switch from favorable disease to HR-NB.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 1 1%
Luxembourg 1 1%
Unknown 66 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 25%
Student > Master 8 12%
Researcher 7 10%
Student > Bachelor 7 10%
Other 5 7%
Other 10 15%
Unknown 14 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 24%
Medicine and Dentistry 13 19%
Agricultural and Biological Sciences 11 16%
Engineering 3 4%
Computer Science 2 3%
Other 7 10%
Unknown 16 24%
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 20 April 2015.
All research outputs
#15,329,087
of 22,799,071 outputs
Outputs from Stem Cell Research & Therapy
#1,340
of 2,418 outputs
Outputs of similar age
#150,792
of 254,702 outputs
Outputs of similar age from Stem Cell Research & Therapy
#23
of 39 outputs
Altmetric has tracked 22,799,071 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,418 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one is in the 34th percentile – i.e., 34% 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 254,702 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 39 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.