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The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells

Overview of attention for article published in Molecular Cancer, November 2015
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Title
The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells
Published in
Molecular Cancer, November 2015
DOI 10.1186/s12943-015-0472-4
Pubmed ID
Authors

Andrea Giannuzzo, Stine Falsig Pedersen, Ivana Novak

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates and least effective treatments. Moreover, total deaths due to PDAC are predicted to increase in the next 15 years. Therefore, novel insights into basic mechanism of PDAC development and therapies are needed. PDAC is characterized by a complex microenvironment, in which cancer and stromal cells release different molecules, such as ATP. ATP can be transported and/or exocytosed from active cancer cells and released from dying cells in the necrotic core of the cancer. We hypothesized that one of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour. We determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human pancreatic duct epithelial cell line (HPDE). The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. Furthermore, we studied P2X7R-dependent pore formation (YoPro-1 assay) and cell death (caspase and annexin V / propidium iodide assays). We found higher expression of P2X7R protein in PDAC compared to HPDE cells. P2X7R had notable disparate effects on PDAC survival. Firstly, high concentrations of ATP or the specific P2X7R agonist, BzATP, had cytotoxic effects in all cell lines, and cell death was mediated by necrosis. Moreover, the P2X7R-pore antagonist, A438079, prevented ATP-induced pore formation and cell death. Second, in basal conditions and with low concentrations of ATP/BzATP, the P2X7R allosteric inhibitor AZ10606120 reduced proliferation in all PDAC cell lines. P2X7R also affected other key characteristics of cancer cell behavior. AZ10606120 reduced cell migration and invasion in PDAC cell lines compared to that of untreated/vehicle-treated control cells, and stimulation with sub-millimolar concentrations of ATP or BzATP substantially increased cell invasion. PDAC cell lines overexpress P2X7R and the receptor plays crucial roles in cell survival, migration and invasion. Therefore, we propose that drugs targeting P2X7R could be exploited in therapy of pancreatic cancer.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 82 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 15 18%
Student > Ph. D. Student 14 17%
Researcher 12 15%
Student > Master 12 15%
Other 5 6%
Other 8 10%
Unknown 16 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 20%
Agricultural and Biological Sciences 13 16%
Medicine and Dentistry 11 13%
Pharmacology, Toxicology and Pharmaceutical Science 7 9%
Immunology and Microbiology 4 5%
Other 12 15%
Unknown 19 23%

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 07 December 2015.
All research outputs
#5,713,941
of 6,690,562 outputs
Outputs from Molecular Cancer
#565
of 663 outputs
Outputs of similar age
#226,523
of 280,760 outputs
Outputs of similar age from Molecular Cancer
#34
of 43 outputs
Altmetric has tracked 6,690,562 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 663 research outputs from this source. They receive a mean Attention Score of 3.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.