Evidence map›Paper›PMID 25386176›Full record

ArticleFrontiers in immunology2014

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

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

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 39 citations in OpenAlex.

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  14. Extracellular Vesicles Enhance Multiple Myeloma Metastatic Dissemination.International journal of molecular sciences · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Giuseppe Di NotoDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
Marco ChiariniCREA, Diagnostic Department, Azienda Ospedaliera Spedali Civili di Brescia , Brescia , Italy.
Lucia PaoliniDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
Elena Laura MazzoldiDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
Viviana GiustiniCREA, Diagnostic Department, Azienda Ospedaliera Spedali Civili di Brescia , Brescia , Italy.
Annalisa RadeghieriDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
Luigi CaimiDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
Doris RicottaDepartment of Molecular and Translational Medicine, Faculty of Medicine, University of Brescia , Brescia , Italy.
University of Brescia · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

extracellular vesiclesglycosaminoglicansmultiple myelomaNfκBserum-free light chain

Identifiers

PMID25386176
PMCPMC4209816
OpenAlexW2149738771

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.