Evidence map›Paper›PMID 25909161›Full record

ArticleOncotarget2015

TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model.

Hendrik Fritsche, Thorsten Heilmann, Robert J Tower, Charlotte Hauser, Anja von Au, Doaa El-Sheikh, Graeme M Campbell, Göhkan Alp, Denis Schewe, Sebastian Hübner and 11 more

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

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

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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

21 authors at 4 institutions in 1 country.

Hendrik FritscheDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Thorsten HeilmannDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Robert J TowerSection Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
Charlotte HauserClinic for General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Anja von AuDepartment of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
Doaa El-SheikhDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Graeme M CampbellSection Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
Göhkan AlpDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Denis ScheweDepartment of General Pediatrics, ALL-BFM Study Group, University Hospital Schleswig-Holstein, Kiel, Germany.
Sebastian HübnerDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Sanjay TiwariSection Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
Daniel KownatzkiDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Susann BoretiusSection Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
Dieter AdamInstitute of Immunology, University of Kiel, Kiel, Germany.
Walter JonatDepartment of Gynecology, University Hospital Schleswig-Holstein, Kiel, Germany.
Thomas BeckerClinic for General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Claus C GlüerSection Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.
Margot ZöllerDepartment of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
Holger KalthoffDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
Christian SchemDepartment of Gynecology, University Hospital Schleswig-Holstein, Kiel, Germany.
Anna TrauzoldDivision of Molecular Oncology, Institute for Experimental Cancer Research, CCC-North, University of Kiel, Kiel, Germany.
University Hospital Schleswig-Holstein · DEUniversity of Lübeck · DEHeidelberg University · DEKiel University · DE

Funding

Tufts Clinical and Translational Research InstituteKL2TR001063 · NCATS · TUFTS UNIVERSITY BOSTON · PI SELKER, HARRY P. · 2013 to 2017
$2.1M
NCATS NIH HHS KL2 TR001063
6 · The paper itself

Abstract

Despite improvements in detection, surgical approaches and systemic therapies, breast cancer remains typically incurable once distant metastases occur. High expression of TRAIL-R2 was found to be associated with poor prognostic parameters in breast cancer patients, suggesting an oncogenic function of this receptor. In the present study, we aimed to determine the impact of TRAIL-R2 on breast cancer metastasis. Using an osteotropic variant of MDA-MB-231 breast cancer cells, we examine the effects of TRAIL-R2 knockdown in vitro and in vivo. Strikingly, in addition to the reduced levels of the proliferation-promoting factor HMGA2 and corresponding inhibition of cell proliferation, knockdown of TRAIL-R2 increased the levels of E-Cadherin and decreased migration. In vivo, these cells were strongly impaired in their ability to form bone metastases after intracardiac injection. Evaluating possible underlying mechanisms revealed a strong downregulation of CXCR4, the receptor for the chemokine SDF-1 important for homing of cancers cells to the bone. In accordance, cell migration towards SDF-1 was significantly impaired by TRAIL-R2 knockdown. Conversely, overexpression of TRAIL-R2 upregulated CXCR4 levels and enhanced SDF-1-directed migration. We therefore postulate that inhibition of TRAIL-R2 expression could represent a promising therapeutic strategy leading to an effective impairment of breast cancer cell capability to form skeletal metastases.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsBone NeoplasmsCadherinsCarcinomaCell DivisionCell Line, TumorChemokine CXCL12ChemotaxisFemaleHeterograftsHMGA2 ProteinHumansMiceMice, SCIDMolecular Targeted TherapyAKT1 protein, humanCadherinsChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanHMGA2 ProteinNeoplasm ProteinsProtein IsoformsProto-Oncogene Proteins c-aktReceptors, CXCR4Receptors, TNF-Related Apoptosis-Inducing LigandRNA, Small InterferingTNFRSF10B protein, humanbone homingbone metastasisbreast cancerCXCR4TRAIL-R2

Identifiers

PMID25909161
PMCPMC4496234
OpenAlexW1807390963

What OpenQuestion holds

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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.