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Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence

Overview of attention for article published in Cell Communication and Signaling, August 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (76th percentile)
  • High Attention Score compared to outputs of the same age and source (92nd percentile)

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1 blog
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73 Mendeley
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Title
Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence
Published in
Cell Communication and Signaling, August 2018
DOI 10.1186/s12964-018-0259-5
Pubmed ID
Authors

Samir Tivari, Haiyan Lu, Tanya Dasgupta, Mariana S. De Lorenzo, Robert Wieder

Abstract

Dormant estrogen receptor positive (ER+) breast cancer micrometastases in the bone marrow survive adjuvant chemotherapy and recur stochastically for more than 20 years. We hypothesized that inflammatory cytokines produced by stromal injury can re-awaken dormant breast cancer cells. We used an established in vitro dormancy model of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells incubated at clonogenic density on fibronectin-coated plates to determine the effects of inflammatory cytokines on reactivation of dormant ER+ breast cancer cells. We measured induction of a mesenchymal phenotype, motility and the capacity to re-enter dormancy. We induced secretory senescence in murine stromal monolayers by oxidation, hypoxia and estrogen deprivation with hydrogen peroxide (H2O2), carbonyl-cyanide m-chlorophenylhydrazzone (CCCP) and Fulvestrant (ICI 182780), respectively, and determined the effects on growth of co-cultivated breast cancer cells. Exogenous recombinant human (rh) interleukin (IL)-6, IL-8 or transforming growth factor β1 (TGFβ1) induced regrowth of dormant MCF-7 cells on fibronectin-coated plates. Dormant cells had decreased expression of E-cadherin and estrogen receptor α (ERα) and increased expression of N-cadherin and SNAI2 (SLUG). Cytokine or TGFβ1 treatment of dormant clones induced formation of growing clones, a mesenchymal appearance, increased motility and an impaired capacity to re-enter dormancy. Stromal injury induced secretion of IL-6, IL-8, upregulated tumor necrosis factor alpha (TNFα), activated TGFβ and stimulated the growth of co-cultivated MCF-7 cells. MCF-7 cells induced secretion of IL-6 and IL-8 by stroma in co-culture. Dormant ER+ breast cancer cells have activated epithelial mesenchymal transition (EMT) gene expression programs and downregulated ERα but maintain a dormant epithelial phenotype. Stromal inflammation reactivates these cells, induces growth and a mesenchymal phenotype. Reactivated, growing cells have an impaired ability to re-enter dormancy. In turn, breast cancer cells co-cultured with stroma induce secretion of IL-6 and IL-8 by the stroma, creating a positive feedback loop.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 73 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 16%
Student > Ph. D. Student 11 15%
Student > Master 8 11%
Student > Bachelor 6 8%
Student > Doctoral Student 4 5%
Other 7 10%
Unknown 25 34%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 30%
Medicine and Dentistry 6 8%
Engineering 5 7%
Agricultural and Biological Sciences 4 5%
Immunology and Microbiology 4 5%
Other 4 5%
Unknown 28 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 19 October 2018.
All research outputs
#3,983,929
of 23,100,534 outputs
Outputs from Cell Communication and Signaling
#79
of 1,021 outputs
Outputs of similar age
#76,754
of 333,251 outputs
Outputs of similar age from Cell Communication and Signaling
#2
of 28 outputs
Altmetric has tracked 23,100,534 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,021 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done particularly well, scoring higher than 92% of its peers.
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 333,251 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.