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Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state

Overview of attention for article published in Stem Cell Research & Therapy, November 2017
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Title
Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state
Published in
Stem Cell Research & Therapy, November 2017
DOI 10.1186/s13287-017-0709-9
Pubmed ID
Authors

Ahmed El-Badawy, Mohamed A. Ghoneim, Mahmoud M. Gabr, Radwa Ayman Salah, Ihab K. Mohamed, Marwa Amer, Nagwa El-Badri

Abstract

Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs). The effect of soluble factors secreted from MCF7, Hela, and HepG2 cancer cell lines on BM-MSCs was assessed using a Transwell indirect coculture system. After 5 days of coculture, BM-MSCs were characterized by flow cytometry for surface marker expression, by qPCR for gene expression profile, and by confocal immunofluorescence for marker expression. We then measured the sensitivity of cocultured BM-MSCs to chemotherapeutic agents, their cell cycle profile, and their response to DNA damage. The sphere formation, invasive properties, and in-vivo performance of BM-MSCs after coculture with cancer cells were also measured. Indirect coculture of cancer cells and BM-MSCs, without direct cell contact, generated slow cycling, chemoresistant spheroid stem cells that highly expressed markers of pluripotency, cancer cells, and cancer stem cells (CSCs). They also displayed properties of a side population and enhanced sphere formation in culture. Accordingly, these cells were termed cancer-induced stem cells (CiSCs). CiSCs showed a more mesenchymal phenotype that was further augmented upon TGF-β stimulation and demonstrated a high expression of the β-catenin pathway and ALDH1A1. These findings demonstrate that MSCs, recruited to the tumor microenvironment in large numbers, may display cellular plasticity, acquire a more stem-like state, and acquire some properties of CSCs upon exposure to cancer cell-secreted factors. These acquired characteristics may contribute to tumor progression, survival, and metastasis. Our findings provide new insights into the interactions between MSCs and cancer cells, with the potential to identify novel molecular targets for cancer therapy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 13 25%
Student > Ph. D. Student 8 15%
Student > Master 5 10%
Student > Doctoral Student 3 6%
Professor 3 6%
Other 11 21%
Unknown 9 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 42%
Medicine and Dentistry 9 17%
Social Sciences 2 4%
Unspecified 1 2%
Agricultural and Biological Sciences 1 2%
Other 3 6%
Unknown 14 27%
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 08 November 2017.
All research outputs
#18,576,001
of 23,007,887 outputs
Outputs from Stem Cell Research & Therapy
#1,740
of 2,429 outputs
Outputs of similar age
#253,908
of 331,365 outputs
Outputs of similar age from Stem Cell Research & Therapy
#63
of 85 outputs
Altmetric has tracked 23,007,887 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 2,429 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 15th percentile – i.e., 15% 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 331,365 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.