Evidence map›Paper›PMID 31548301›Full record

ArticleThe Journal of experimental medicine2019

Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis.

Jinlu Dai, June Escara-Wilke, Jill M Keller, Younghun Jung, Russell S Taichman, Kenneth J Pienta, Evan T Keller

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 3 pooled it
8.4field-weighted citation impact, top 2% 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

121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 169 citations in OpenAlex.

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61 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

Jinlu DaiDepartment of Urology, Medical School, University of Michigan, Ann Arbor, MI.
June Escara-WilkeDepartment of Urology, Medical School, University of Michigan, Ann Arbor, MI.
Jill M KellerDepartment of Urology, Medical School, University of Michigan, Ann Arbor, MI.
Younghun JungPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI.
Russell S TaichmanPeriodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI.ORCID 0000-0002-7890-0020
Kenneth J PientaDepartment of Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, MD.ORCID 0000-0002-4138-2186
Evan T KellerDepartment of Urology, Medical School, University of Michigan, Ann Arbor, MI etkeller@umich.edu.ORCID 0000-0002-7592-7535
University of Michigan · USJohns Hopkins University · US

Funding

Tumor microvesicle-mediated modulation of the bone microenvironmentP01CA093900 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J. · 2004 to 2024
$29.6M
NCI NIH HHS P01 CA093900
6 · The paper itself

Abstract

Prostate cancer (PCa) metastasizes selectively to bone through unknown mechanisms. In the current study, we identified exosome-mediated transfer of pyruvate kinase M2 (PKM2) from PCa cells into bone marrow stromal cells (BMSCs) as a novel mechanism through which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in a HIF-1α-dependent fashion, which subsequently enhances PCa seeding and growth in the bone marrow. Furthermore, serum-derived exosomes from patients with either primary PCa or PCa metastasis, as opposed to healthy men, reveal that increased exosome PKM2 expression is associated with metastasis, suggesting clinical relevance of exosome PKM2 in PCa. Targeting the exosome-induced CXCL12 axis diminished exosome-mediated bone metastasis. In summary, primary PCa cells educate the bone marrow to create a premetastatic niche through primary PCa exosome-mediated transfer of PKM2 into BMSCs and subsequent up-regulation of CXCL12. This novel mechanism indicates the potential for exosome PKM2 as a biomarker and suggests therapeutic targets for PCa bone metastasis.

Indexed as

AnimalsBone NeoplasmsCell Line, TumorCell MovementCell ProliferationChemokine CXCL12Disease Models, AnimalExosomesGene ExpressionHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceModels, BiologicalProstatic NeoplasmsPyruvate KinaseChemokine CXCL12Hypoxia-Inducible Factor 1, alpha SubunitPyruvate Kinase

Identifiers

PMID31548301
PMCPMC6888980
OpenAlexW2976085893

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.