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Alternagin-C binding to α2β1 integrin controls matrix metalloprotease-9 and matrix metalloprotease-2 in breast tumor cells and endothelial cells

Overview of attention for article published in Journal of Venomous Animals and Toxins including Tropical Diseases, April 2018
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Title
Alternagin-C binding to α2β1 integrin controls matrix metalloprotease-9 and matrix metalloprotease-2 in breast tumor cells and endothelial cells
Published in
Journal of Venomous Animals and Toxins including Tropical Diseases, April 2018
DOI 10.1186/s40409-018-0150-2
Pubmed ID
Authors

Milene Nóbrega de Oliveira Moritz, Lívia Mara Santos Eustáquio, Kelli Cristina Micocci, Ana Carolina Caetano Nunes, Patty Karina dos Santos, Tamires de Castro Vieira, Heloísa Sobreiro Selistre-de-Araujo

Abstract

Matrix metalloproteinases (MMPs) are key players in tumor progression, helping tumor cells to modify their microenvironment, which allows cell migration to secondary sites. The role of integrins, adhesion receptors that connect cells to the extracellular matrix, in MMP expression and activity has been previously suggested. However, the mechanisms by which integrins control MMP expression are not completely understood. Particularly, the role of α2β1 integrin, one of the major collagen I receptors, in MMP activity and expression has not been studied. Alternagin-C (ALT-C), a glutamate-cysteine-aspartate-disintegrin from Bothrops alternatus venom, has high affinity for an α2β1 integrin. Herein, we used ALT-C as a α2β1 integrin ligand to study the effect of ALT-C on MMP-9 and MMP-2 expression as well as on tumor cells, fibroblats and endothelial cell migration. ALT-C was purified by two steps of gel filtration followed by anion exchange chromatography. The α2β1 integrin binding properties of ALT-C, its dissociation constant (K d ) relative to this integrin and to collagen I (Col I) were determined by surface plasmon resonance. The effects of ALT-C (10, 40, 100 and 1000 nM) in migration assays were studied using three human cell lines: human fibroblasts, breast tumor cell line MDA-MB-231, and microvascular endothelial cells HMEC-1, considering cells found in the tumor microenvironment. ALT-C effects on MMP-9 and MMP-2 expression and activity were analyzed by quantitative PCR and gelatin zymography, respectively. Focal adhesion kinase activation was determined by western blotting. Our data demonstrate that ALT-C, after binding to α2β1 integrin, acts by two distinct mechanisms against tumor progression, depending on the cell type: in tumor cells, ALT-C decreases MMP-9 and MMP-2 contents and activity, but increases focal adhesion kinase phosphorylation and transmigration; and in endothelial cells, ALT-C inhibits MMP-2, which is necessary for tumor angiogenesis. ALT-C also upregulates c-Myc mRNA level, which is related to tumor suppression. These results demonstrate that α2β1 integrin controls MMP expression and reveal this integrin as a target for the development of antiangiogenic and antimetastatic 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 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 2 15%
Student > Ph. D. Student 2 15%
Professor 1 8%
Student > Bachelor 1 8%
Student > Master 1 8%
Other 1 8%
Unknown 5 38%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 23%
Agricultural and Biological Sciences 1 8%
Medicine and Dentistry 1 8%
Unknown 8 62%

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 16 May 2018.
All research outputs
#9,916,502
of 12,953,232 outputs
Outputs from Journal of Venomous Animals and Toxins including Tropical Diseases
#223
of 332 outputs
Outputs of similar age
#189,429
of 271,120 outputs
Outputs of similar age from Journal of Venomous Animals and Toxins including Tropical Diseases
#1
of 1 outputs
Altmetric has tracked 12,953,232 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 332 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 16th percentile – i.e., 16% 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 271,120 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them