Evidence map›Paper›PMID 26806351›Full record

ArticleNeoplasia (New York, N.Y.)2016

Targeting of CCL2-CCR2-Glycosaminoglycan Axis Using a CCL2 Decoy Protein Attenuates Metastasis through Inhibition of Tumor Cell Seeding.

Marko Roblek, Elisabeth Strutzmann, Christina Zankl, Tiziana Adage, Mathias Heikenwalder, Aid Atlic, Roland Weis, Andreas Kungl, Lubor Borsig

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  8. Comparing the Cytokine Storms of COVID-19 and Pandemic Influenza.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. CCL2 in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021
    Article
  15. Review
  16. Review
  17. Article
  18. Review
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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

9 authors at 3 institutions in 3 countries.

Marko RoblekInstitute of Physiology, University of Zürich and Zürich Center for Integrative Human Physiology, CH-8057 Zurich, Switzerland.
Elisabeth StrutzmannKF-University Graz, Graz Austria.
Christina ZanklKF-University Graz, Graz Austria.
Tiziana AdageProtAffin Biotechnologie AG, Graz Austria.
Mathias HeikenwalderInstitute of Virology, Technische Universität München/Helmholtz Zentrum Munich für Gesundheit und Umwelt, Munich, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Aid AtlicVTU Technology GmbH, Grambach, Austria.
Roland WeisVTU Technology GmbH, Grambach, Austria.
Andreas KunglKF-University Graz, Graz Austria; ProtAffin Biotechnologie AG, Graz Austria; Antagonis Biotherapeutics, Graz Austria.
Lubor BorsigInstitute of Physiology, University of Zürich and Zürich Center for Integrative Human Physiology, CH-8057 Zurich, Switzerland. Electronic address: lborsig@access.uzh.ch.
University of Zurich · CHBioTechMed-Graz · ATGerman Cancer Research Center · DE

Funding

Swiss National Science Foundation 136033
6 · The paper itself

Abstract

The CCL2-CCR2 chemokine axis has an important role in cancer progression where it contributes to metastatic dissemination of several cancer types (e.g., colon, breast, prostate). Tumor cell-derived CCL2 was shown to promote the recruitment of CCR2(+)/Ly6C(hi) monocytes and to induce vascular permeability of CCR2(+) endothelial cells in the lungs. Here we describe a novel decoy protein consisting of a CCL2 mutant protein fused to human serum albumin (dnCCL2-HSA chimera) with enhanced binding affinity to glycosaminoglycans that was tested in vivo. The monocyte-mediated tumor cell transendothelial migration was strongly reduced upon unfused dnCCL2 mutant treatment in vitro. dnCCL2-HSA chimera had an extended serum half-life and thus a prolonged exposure in vivo compared with the dnCCL2 mutant. dnCCL2-HSA chimera bound to the lung vasculature but caused minimal alterations in the leukocyte recruitment to the lungs. However, dnCCL2-HSA chimera treatment strongly reduced both lung vascular permeability and tumor cell seeding. Metastasis of MC-38GFP, 3LL, and LLC1 cells was significantly attenuated upon dnCCL2-HSA chimera treatment. Tumor cell seeding to the lungs resulted in enhanced expression of a proteoglycan syndecan-4 by endothelial cells that correlated with accumulation of the dnCCL2-HSA chimera in the vicinity of tumor cells. These findings demonstrate that the CCL2-based decoy protein effectively binds to the activated endothelium in lungs and blocks tumor cell extravasation through inhibition of vascular permeability.

Indexed as

AnimalsCell Line, TumorCell MovementChemokine CCL2Disease Models, AnimalDisease ProgressionGene ExpressionGlycosaminoglycansHumansLung NeoplasmsMaleMiceNeoplasm MetastasisNeoplasmsReceptors, CCR2Recombinant ProteinsChemokine CCL2GlycosaminoglycansReceptors, CCR2Recombinant ProteinsSyndecan-4

Identifiers

PMID26806351
PMCPMC4735630
OpenAlexW2254564403

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.