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Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation

Overview of attention for article published in BMC Cancer, January 2015
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  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

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Title
Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation
Published in
BMC Cancer, January 2015
DOI 10.1186/s12885-015-1023-5
Pubmed ID
Authors

Cinzia Fionda, Maria Pia Abruzzese, Alessandra Zingoni, Alessandra Soriani, Biancamaria Ricci, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli

Abstract

BackgroundDNAX accessory molecule-1 (DNAM-1) is an activating receptor constitutively expressed by macrophages/dendritic cells and by T lymphocytes and Natural Killer (NK) cells, having an important role in anticancer responses; in this regard, combination therapies able to enhance the expression of DNAM-1 ligands on tumor cells are of therapeutic interest. In this study, we investigated the effect of different nitric oxide (NO) donors on the expression of the DNAM-1 ligand Poliovirus Receptor/CD155 (PVR/CD155) in multiple myeloma (MM) cells.MethodsSix MM cell lines, SKO-007(J3), U266, OPM-2, RPMI-8226, ARK and LP1 were used to investigate the activity of different nitric oxide donors [DETA-NO and the NO-releasing prodrugs NCX4040 (NO-aspirin) and JS-K] on the expression of PVR/CD155, using Flow Cytometry and Real-Time PCR. Western-blot and specific inhibitors were employed to investigate the role of soluble guanylyl cyclase/cGMP and activation of the DNA damage response (DDR).ResultsOur results indicate that increased levels of nitric oxide can upregulate PVR/CD155 cell surface and mRNA expression in MM cells; in addition, exposure to nitric oxide donors renders myeloma cells more efficient to activate NK cell degranulation and enhances their ability to trigger NK cell-mediated cytotoxicity. We found that activation of the soluble guanylyl cyclase and increased cGMP concentrations by nitric oxide is not involved in the up-regulation of ligand expression. On the contrary, treatment of MM cells with nitric oxide donors correlated with the activation of a DNA damage response pathway and inhibition of the ATM /ATR/Chk1/2 kinase activities by specific inhibitors significantly abrogates up-regulation.ConclusionsThe present study provide evidence that regulation of the PVR/CD155 DNAM-1 ligand expression by nitric oxide may represent an additional immune-mediated mechanism and support the anti-myeloma activity of nitric oxide donors.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 28%
Student > Bachelor 9 19%
Student > Ph. D. Student 7 15%
Student > Doctoral Student 2 4%
Other 1 2%
Other 2 4%
Unknown 13 28%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 19%
Immunology and Microbiology 8 17%
Biochemistry, Genetics and Molecular Biology 7 15%
Medicine and Dentistry 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 4 9%
Unknown 13 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 17 December 2019.
All research outputs
#6,277,372
of 22,778,347 outputs
Outputs from BMC Cancer
#1,565
of 8,288 outputs
Outputs of similar age
#86,282
of 351,834 outputs
Outputs of similar age from BMC Cancer
#29
of 132 outputs
Altmetric has tracked 22,778,347 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 8,288 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 80% 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 351,834 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 132 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.