Evidence map›Paper›PMID 26100252›Full record

ArticleBlood2015

Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts.

Jerome Paggetti, Franziska Haderk, Martina Seiffert, Bassam Janji, Ute Distler, Wim Ammerlaan, Yeoun Jin Kim, Julien Adam, Peter Lichter, Eric Solary and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 295 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
295citing papers in PubMed, 1 pooled it
21.2field-weighted citation impact, top 1% 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

295 citing papers in PubMed, 1 synthesis or guideline pooled it, 451 citations in OpenAlex.

  1. Guideline
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235 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Jerome PaggettiLaboratory of Experimental Hemato-Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg;
Franziska HaderkDepartment for Molecular Genetics, German Cancer Research Center, Heidelberg, Germany;
Martina SeiffertDepartment for Molecular Genetics, German Cancer Research Center, Heidelberg, Germany;
Bassam JanjiLaboratory of Experimental Hemato-Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg;
Ute DistlerLuxembourg Clinical Proteomics Center, Luxembourg Institute of Health, Luxembourg, Luxembourg;
Wim AmmerlaanIntegrated BioBank of Luxembourg, Luxembourg, Luxembourg;
Yeoun Jin KimLuxembourg Clinical Proteomics Center, Luxembourg Institute of Health, Luxembourg, Luxembourg;
Julien AdamINSERM U981, Gustave Roussy, Villejuif, France; Faculty of Medicine, University Paris-Sud, Le Kremlin-Bicêtre, France;
Peter LichterDepartment for Molecular Genetics, German Cancer Research Center, Heidelberg, Germany;
Eric SolaryFaculty of Medicine, University Paris-Sud, Le Kremlin-Bicêtre, France; INSERM UMR1009, Gustave Roussy Villejuif, France; and.
Guy BerchemLaboratory of Experimental Hemato-Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg; Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
Etienne MoussayLaboratory of Experimental Hemato-Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg;
Luxembourg Institute of Health · LUGerman Cancer Research Center · DEUniversité Paris-Sud · FRCentral Bank of Luxembourg · LUHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exosomes derived from solid tumor cells are involved in immune suppression, angiogenesis, and metastasis, but the role of leukemia-derived exosomes has been less investigated. The pathogenesis of chronic lymphocytic leukemia (CLL) is stringently associated with a tumor-supportive microenvironment and a dysfunctional immune system. Here, we explore the role of CLL-derived exosomes in the cellular and molecular mechanisms by which malignant cells create this favorable surrounding. We show that CLL-derived exosomes are actively incorporated by endothelial and mesenchymal stem cells ex vivo and in vivo and that the transfer of exosomal protein and microRNA induces an inflammatory phenotype in the target cells, which resembles the phenotype of cancer-associated fibroblasts (CAFs). As a result, stromal cells show enhanced proliferation, migration, and secretion of inflammatory cytokines, contributing to a tumor-supportive microenvironment. Exosome uptake by endothelial cells increased angiogenesis ex vivo and in vivo, and coinjection of CLL-derived exosomes and CLL cells promoted tumor growth in immunodeficient mice. Finally, we detected α-smooth actin-positive stromal cells in lymph nodes of CLL patients. These findings demonstrate that CLL-derived exosomes actively promote disease progression by modulating several functions of surrounding stromal cells that acquire features of cancer-associated fibroblasts.

Indexed as

AgedAged, 80 and overCells, CulturedCell SurvivalExosomesFibroblastsHumansInflammationLeukemia, Lymphocytic, Chronic, B-CellMicroRNAsMiddle AgedNeovascularization, PathologicProtein TransportSignal TransductionStromal CellsMicroRNAs

Identifiers

PMID26100252
PMCPMC4560344
OpenAlexW1638318949

What OpenQuestion holds

Textmetadata
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.