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Proteinase-activated receptor 2 (PAR2) in hepatic stellate cells – evidence for a role in hepatocellular carcinoma growth in vivo

Overview of attention for article published in Molecular Cancer, July 2016
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  • Good Attention Score compared to outputs of the same age (68th percentile)

Mentioned by

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2 tweeters
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1 patent

Citations

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24 Dimensions

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26 Mendeley
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Title
Proteinase-activated receptor 2 (PAR2) in hepatic stellate cells – evidence for a role in hepatocellular carcinoma growth in vivo
Published in
Molecular Cancer, July 2016
DOI 10.1186/s12943-016-0538-y
Pubmed ID
Authors

Franziska Mußbach, Hendrik Ungefroren, Bernd Günther, Kathrin Katenkamp, Petra Henklein, Martin Westermann, Utz Settmacher, Lennart Lenk, Susanne Sebens, Jörg P. Müller, Frank-Dietmar Böhmer, Roland Kaufmann

Abstract

Previous studies have established that proteinase-activated receptor 2 (PAR2) promotes migration and invasion of hepatocellular carcinoma (HCC) cells, suggesting a role in HCC progression. Here, we assessed the impact of PAR2 in HCC stromal cells on HCC growth using LX-2 hepatic stellate cells (HSCs) and Hep3B cells as model. PAR2 expression and function in LX-2 cells was analysed by RT-PCR, confocal immunofluorescence, electron microscopy, and [Ca(2+)]i measurements, respectively. The impact of LX-2-expressed PAR2 on tumour growth in vivo was monitored using HCC xenotransplantation experiments in SCID mice, in which HCC-like tumours were induced by coinjection of LX-2 cells and Hep3B cells. To characterise the effects of PAR2 activation in LX-2 cells, various signalling pathways were analysed by immunoblotting and proteome profiler arrays. Following verification of functional PAR2 expression in LX-2 cells, in vivo studies showed that these cells promoted tumour growth and angiogenesis of HCC xenografts in mice. These effects were significantly reduced when F2RL1 (encoding PAR2) was downregulated by RNA interference (RNAi). In vitro studies confirmed these results demonstrating RNAi mediated inhibition of PAR2 attenuated Smad2/3 activation in response to TGF-β1 stimulation in LX-2 cells and blocked the pro-mitotic effect of LX-2 derived conditioned medium on Hep3B cells. Furthermore, PAR2 stimulation with trypsin or a PAR2-selective activating peptide (PAR2-AP) led to activation of different intracellular signalling pathways, an increased secretion of pro-angiogenic and pro-mitotic factors and proteinases, and an enhanced migration rate across a collagen-coated membrane barrier. Silencing F2RL1 by RNAi or pharmacological inhibition of Src, hepatocyte growth factor receptor (Met), platelet-derived growth factor receptor (PDGFR), p42/p44 mitogen activated protein kinase (MAPK) or matrix-metalloproteinases (MMPs) blocked PAR2-AP-induced migration. PAR2 in HSCs plays a crucial role in promoting HCC growth presumably by mediating migration and secretion of pro-angiogenic and pro-mitotic factors. Therefore, PAR2 in stromal HSCs may have relevance as a therapeutic target of HCC.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters 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 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 31%
Student > Master 5 19%
Student > Ph. D. Student 2 8%
Student > Bachelor 2 8%
Professor 1 4%
Other 3 12%
Unknown 5 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 23%
Medicine and Dentistry 6 23%
Agricultural and Biological Sciences 4 15%
Engineering 2 8%
Neuroscience 1 4%
Other 0 0%
Unknown 7 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 February 2022.
All research outputs
#6,112,943
of 21,851,503 outputs
Outputs from Molecular Cancer
#403
of 1,654 outputs
Outputs of similar age
#86,548
of 280,648 outputs
Outputs of similar age from Molecular Cancer
#1
of 1 outputs
Altmetric has tracked 21,851,503 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 1,654 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has gotten more attention than average, scoring higher than 74% 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 280,648 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
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