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A novel neuregulin – jagged1 paracrine loop in breast cancer transendothelial migration

Overview of attention for article published in Breast Cancer Research, April 2018
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Title
A novel neuregulin – jagged1 paracrine loop in breast cancer transendothelial migration
Published in
Breast Cancer Research, April 2018
DOI 10.1186/s13058-018-0960-8
Pubmed ID
Authors

Ramon M. Cabrera, Serena P. H. Mao, Chinmay R. Surve, John S. Condeelis, Jeffrey E. Segall

Abstract

The interaction of breast cancer cells with other cells in the tumor microenvironment plays an important role in metastasis. Invasion and intravasation, two critical steps in the metastatic process, are influenced by these interactions. Macrophages are of particular interest when it comes to studying tumor cell invasiveness. Previous studies have shown that there is paracrine loop signaling between breast cancer cells and macrophages involving colony stimulating factor 1 (CSF-1) produced by tumor cells and epidermal growth factor (EGF) production by macrophages. In this paper, we identify a novel paracrine loop between tumor cells and macrophages involving neuregulin (NRG1) and notch signaling. The aim of this study was to determine the role of NRG1, a ligand of the ErbB3 receptor, in macrophage stimulation of tumor cell transendothelial migration and intravasation. We used fluorescence-activated cell sorting (FACS) and western blot to determine ErbB3 and NRG1 expression, respectively. An in vitro transendothelial migration (iTEM) assay was used to examine the effects of short hairpin (sh)RNA targeting NRG1 in tumor cells and clustered regularly interspaced short palindromic repeats (CRISPR) knockout of jagged 1 (JAG1) in macrophages. Orthotopic xenograft injections in mice were used to confirm results in vivo. In our system, macrophages were the primary cells showing expression of ErbB3, and a blocking antibody against ErbB3 resulted in a significant decrease in macrophage-induced transendothelial migration of breast cancer cells. Stimulation of macrophages with NRG1 upregulated mRNA and protein expression of JAG1, a ligand of the Notch receptor, and JAG1 production by macrophages was important for transendothelial migration of tumor cells. This study demonstrates that stimulation of macrophages by tumor cell NRG1 can enhance transendothelial migration and intravasation. We also demonstrate that this effect is due to induction of macrophage JAG1, an important ligand of the Notch signaling pathway.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 26%
Researcher 7 16%
Student > Doctoral Student 4 9%
Student > Postgraduate 3 7%
Student > Bachelor 2 5%
Other 6 14%
Unknown 10 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 26%
Agricultural and Biological Sciences 10 23%
Medicine and Dentistry 4 9%
Immunology and Microbiology 3 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 2 5%
Unknown 12 28%
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 24 April 2018.
All research outputs
#20,663,600
of 25,382,440 outputs
Outputs from Breast Cancer Research
#1,708
of 2,054 outputs
Outputs of similar age
#267,891
of 343,274 outputs
Outputs of similar age from Breast Cancer Research
#19
of 23 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 8th percentile – i.e., 8% 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 343,274 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.