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Placental growth factor inhibition modulates the interplay between hypoxia and unfolded protein response in hepatocellular carcinoma

Overview of attention for article published in BMC Cancer, January 2016
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (52nd percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

Mentioned by

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3 tweeters

Citations

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15 Dimensions

Readers on

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20 Mendeley
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Title
Placental growth factor inhibition modulates the interplay between hypoxia and unfolded protein response in hepatocellular carcinoma
Published in
BMC Cancer, January 2016
DOI 10.1186/s12885-015-1990-6
Pubmed ID
Authors

Yves-Paul Vandewynckel, Debby Laukens, Lindsey Devisscher, Eliene Bogaerts, Annelies Paridaens, Anja Van den Bussche, Sarah Raevens, Xavier Verhelst, Christophe Van Steenkiste, Bart Jonckx, Louis Libbrecht, Anja Geerts, Peter Carmeliet, Hans Van Vlierberghe

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. We previously showed that the inhibition of placental growth factor (PlGF) exerts antitumour effects and induces vessel normalisation, possibly reducing hypoxia. However, the exact mechanism underlying these effects remains unclear. Because hypoxia and endoplasmic reticulum stress, which activates the unfolded protein response (UPR), have been implicated in HCC progression, we assessed the interactions between PlGF and these microenvironmental stresses. PlGF knockout mice and validated monoclonal anti-PlGF antibodies were used in a diethylnitrosamine-induced mouse model for HCC. We examined the interactions among hypoxia, UPR activation and PlGF induction in HCC cells. Both the genetic and pharmacological inhibitions of PlGF reduced the chaperone levels and the activation of the PKR-like endoplasmic reticulum kinase (PERK) pathway of the UPR in diethylnitrosamine-induced HCC. Furthermore, we identified that tumour hypoxia was attenuated, as shown by reduced pimonidazole binding. Interestingly, hypoxic exposure markedly activated the PERK pathway in HCC cells in vitro, suggesting that PlGF inhibition may diminish PERK activation by improving oxygen delivery. We also found that PlGF expression is upregulated by different chemical UPR inducers via activation of the inositol-requiring enzyme 1 pathway in HCC cells. PlGF inhibition attenuates PERK activation, likely by tempering hypoxia in HCC via vessel normalisation. The UPR, in turn, is able to regulate PlGF expression, suggesting the existence of a feedback mechanism for hypoxia-mediated UPR that promotes the expression of the angiogenic factor PlGF. These findings have important implications for our understanding of the effect of therapies normalising tumour vasculature.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 5%
Belgium 1 5%
Brazil 1 5%
Unknown 17 85%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 25%
Student > Ph. D. Student 4 20%
Student > Bachelor 2 10%
Student > Doctoral Student 2 10%
Other 1 5%
Other 4 20%
Unknown 2 10%
Readers by discipline Count As %
Medicine and Dentistry 11 55%
Biochemistry, Genetics and Molecular Biology 3 15%
Agricultural and Biological Sciences 2 10%
Neuroscience 1 5%
Chemistry 1 5%
Other 0 0%
Unknown 2 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 13 January 2016.
All research outputs
#3,161,694
of 6,956,879 outputs
Outputs from BMC Cancer
#1,140
of 3,157 outputs
Outputs of similar age
#139,776
of 303,561 outputs
Outputs of similar age from BMC Cancer
#49
of 179 outputs
Altmetric has tracked 6,956,879 research outputs across all sources so far. This one has received more attention than most of these and is in the 53rd percentile.
So far Altmetric has tracked 3,157 research outputs from this source. They receive a mean Attention Score of 3.3. This one has gotten more attention than average, scoring higher than 63% 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 303,561 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 52% of its contemporaries.
We're also able to compare this research output to 179 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.