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Immunoglobulin Free Light Chains and GAGs Mediate Multiple Myeloma Extracellular Vesicles Uptake and Secondary NfκB Nuclear Translocation

Overview of attention for article published in Frontiers in immunology, October 2014
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Title
Immunoglobulin Free Light Chains and GAGs Mediate Multiple Myeloma Extracellular Vesicles Uptake and Secondary NfκB Nuclear Translocation
Published in
Frontiers in immunology, October 2014
DOI 10.3389/fimmu.2014.00517
Pubmed ID
Authors

Giuseppe Di Noto, Marco Chiarini, Lucia Paolini, Elena Laura Mazzoldi, Viviana Giustini, Annalisa Radeghieri, Luigi Caimi, Doris Ricotta

Abstract

Multiple myeloma (MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasma cells in the bone marrow. Monoclonal plasma cells often secrete high amounts of immunoglobulin free light chains (FLCs) that could induce tissue damage. Recently, we showed that FLCs are internalized in endothelial and myocardial cell lines and secreted in extracellular vesicles (EVs). MM serum derived EVs presented phenotypic differences if compared with monoclonal gammopathy of undetermined significance (MGUS) serum derived EVs suggesting their involvement in MM pathogenesis or progression. To investigate the effect of circulating EVs on endothelial and myocardial cells, we purified MM and MGUS serum derived EVs with differential ultracentrifugation protocols and tested their biological activity. We found that MM and MGUS EVs induced different proliferation and internalization rates in endothelial and myocardial cells, thus we tried to find specific targets in MM EVs docking and processing. Pre-treatment of EVs with anti-FLCs antibodies or heparin blocked the MM EVs uptake, highlighting that FLCs and glycosaminoglycans are involved. Indeed, only MM EVs exposure induced a strong nuclear factor kappa B nuclear translocation that was completely abolished after anti-FLCs antibodies and heparin pre-treatment. The protein tyrosine kinase c-src is present on MM circulating EVs and redistributes to the cell plasma membrane after MM EVs exposure. The anti-FLCs antibodies and heparin pre-treatments were able to block the intracellular re-distribution of the c-src kinase and the subsequent c-src kinase containing EVs production. Our results open new insights in EVs cellular biology and in MM therapeutic and diagnostic approaches.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Denmark 1 2%
Unknown 50 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 23%
Student > Ph. D. Student 8 15%
Student > Master 8 15%
Student > Postgraduate 4 8%
Other 4 8%
Other 10 19%
Unknown 6 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 12 23%
Medicine and Dentistry 11 21%
Biochemistry, Genetics and Molecular Biology 10 19%
Immunology and Microbiology 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 11 21%
Unknown 4 8%
Attention Score in Context

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 27 October 2014.
All research outputs
#22,758,309
of 25,371,288 outputs
Outputs from Frontiers in immunology
#27,414
of 31,513 outputs
Outputs of similar age
#233,270
of 273,620 outputs
Outputs of similar age from Frontiers in immunology
#168
of 187 outputs
Altmetric has tracked 25,371,288 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 31,513 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 1st percentile – i.e., 1% 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 273,620 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 187 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.