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Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis supporting the growth of skin papillomas

Overview of attention for article published in BMC Cancer, August 2015
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1 tweeter

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Title
Incomplete Dll4/Notch signaling inhibition promotes functional angiogenesis supporting the growth of skin papillomas
Published in
BMC Cancer, August 2015
DOI 10.1186/s12885-015-1605-2
Pubmed ID
Authors

Dusan Djokovic, Alexandre Trindade, Joana Gigante, Mario Pinho, Adrian L. Harris, Antonio Duarte

Abstract

In invasive malignancies, Dll4/Notch signaling inhibition enhances non-functional vessel proliferation and limits tumor growth by reducing its blood perfusion. To assess the effects of targeted Dll4 allelic deletion in the incipient stages of tumor pathogenesis, we chemically induced skin papillomas in wild-type and Dll4 (+/-) littermates, and compared tumor growth, their histological features, vascularization and the expression of angiogenesis-related molecules. We observed that Dll4 down-regulation promotes productive angiogenesis, although with less mature vessels, in chemically-induced pre-cancerous skin papillomas stimulating their growth. The increase in endothelial activation was associated with an increase in the VEGFR2 to VEGFR1 ratio, which neutralized the tumor-suppressive effect of VEGFR-targeting sorafenib. Thus, in early papillomas, lower levels of Dll4 increase vascularization through raised VEGFR2 levels, enhancing sensitivity to endogenous levels of VEGF, promoting functional angiogenesis and tumor growth. Tumor promoting effect of low-dosage inhibition needs to be considered when implementing Dll4 targeting therapies.

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 %
Researcher 3 15%
Professor 3 15%
Student > Ph. D. Student 3 15%
Other 3 15%
Student > Master 2 10%
Other 3 15%
Unknown 3 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 20%
Biochemistry, Genetics and Molecular Biology 4 20%
Medicine and Dentistry 3 15%
Immunology and Microbiology 3 15%
Unspecified 1 5%
Other 2 10%
Unknown 3 15%

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 28 August 2015.
All research outputs
#3,921,107
of 5,560,729 outputs
Outputs from BMC Cancer
#1,889
of 2,971 outputs
Outputs of similar age
#134,413
of 194,919 outputs
Outputs of similar age from BMC Cancer
#110
of 147 outputs
Altmetric has tracked 5,560,729 research outputs across all sources so far. This one is in the 16th percentile – i.e., 16% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,971 research outputs from this source. They receive a mean Attention Score of 2.9. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
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We're also able to compare this research output to 147 others from the same source and published within six weeks on either side of this one. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.