Evidence map›Paper›PMID 25178650›Full record

ArticleNature communications2014

Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis.

Esak Lee, Elana J Fertig, Kideok Jin, Saraswati Sukumar, Niranjan B Pandey, Aleksander S Popel

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

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 2 pooled it
6.3field-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

130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 197 citations in OpenAlex.

  1. Pooled it
  2. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019
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70 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

6 authors at 3 institutions in 1 country.

Esak Lee1] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Chemical and Biomolecular Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Elana J FertigDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Kideok JinDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Saraswati SukumarDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Niranjan B PandeyDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Aleksander S Popel1] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Chemical and Biomolecular Engineering, School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA [3] Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Johns Hopkins University · USJohns Hopkins Medicine · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Predictive experiment-based multiscale models of the tumor immune microenvironment and immunotherapy in breast cancerR01CA138264 · NCI · JOHNS HOPKINS UNIVERSITY · PI POPEL, ALEKSANDER S. · 2009 to 2023
$8.1M
Identifying Malignant Cell Signaling from Protein Interactions an Polyomic DataK25CA141053 · NCI · JOHNS HOPKINS UNIVERSITY · PI FERTIG, ELANA · 2010 to 2014
$419k
NCI NIH HHS CA141053NCI NIH HHS K25 CA141053NCI NIH HHS R01 CA138264
6 · The paper itself

Abstract

Breast cancer metastasis involves lymphatic dissemination in addition to hematogenous spreading. Although stromal lymphatic vessels (LVs) serve as initial metastatic routes, roles of organ-residing LVs are underinvestigated. Here we show that lymphatic endothelial cells (LECs), a component of LVs within pre-metastatic niches, are conditioned by triple-negative breast cancer (TNBC) cells to accelerate metastasis. LECs within the lungs and lymph nodes, conditioned by tumour-secreted factors, express CCL5 that is not expressed either in normal LECs or in cancer cells, and direct tumour dissemination into these tissues. Moreover, tumour-conditioned LECs promote angiogenesis in these organs, allowing tumour extravasation and colonization. Mechanistically, tumour cell-secreted IL6 causes Stat3 phosphorylation in LECs. This pStat3 induces HIF-1α and VEGF, and a pStat3-pc-Jun-pATF-2 ternary complex induces CCL5 expression in LECs. This study demonstrates anti-metastatic activities of multiple repurposed drugs, blocking a self-reinforcing paracrine loop between breast cancer cells and LECs.

Indexed as

Aminosalicylic AcidsAnimalsAntibodies, NeutralizingBenzenesulfonatesCell AdhesionCell Line, TumorCell MovementCell ProliferationChemokine CCL5Culture Media, ConditionedCyclohexanesFemaleGene ExpressionHumansHuman Umbilical Vein Endothelial CellsHypoxia-Inducible Factor 1, alpha SubunitAminosalicylic AcidsAntibodies, NeutralizingBenzenesulfonatesChemokine CCL5Culture Media, ConditionedCyclohexanesHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIL6 protein, humanInterleukin-6Interleukin-6 InhibitorsMaravirocNSC 74859STAT3 protein, humanSTAT3 Transcription FactorTriazolesVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID25178650
PMCPMC4351998
OpenAlexW2001868807

What OpenQuestion holds

Textmetadata
LicenceTDM
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.