Evidence map›Paper›PMID 29706656›Full record

ArticleOncogene2018

The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth.

Raimond Heukers, Tian Shu Fan, Raymond H de Wit, Jeffrey R van Senten, Timo W M De Groof, Maarten P Bebelman, Tonny Lagerweij, Joao Vieira, Sabrina M de Munnik, Laura Smits-de Vries and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026
    Review
  4. Review
  5. Article
  6. Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  7. Review
  8. Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. G protein-coupled receptors: a gateway to targeting oncogenic EVs?Extracellular vesicles and circulating nucleic acids · 2024
    Review
  17. Article
  18. Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  19. Article
  20. Review
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

19 authors at 4 institutions in 3 countries.

Raimond HeukersAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Tian Shu FanAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Raymond H de WitAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Jeffrey R van SentenAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Timo W M De GroofAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Maarten P BebelmanAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Tonny LagerweijNeuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.ORCID http://orcid.org/0000-0003-1043-7452
Joao VieiraAblynx N.V., Technologiepark 21, Zwijnaarde, 9052, Belgium.
Sabrina M de MunnikAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Laura Smits-de VriesAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Jody van OffenbeekAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Afsar RahbarDepartment of Medicine Solna, Experimental Cardiovascular Research Unit and Department of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institute, Stockholm, 171 77, Sweden.
Diane van HoorickAblynx N.V., Technologiepark 21, Zwijnaarde, 9052, Belgium.
Cecilia Söderberg-NauclerDepartment of Medicine Solna, Experimental Cardiovascular Research Unit and Department of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institute, Stockholm, 171 77, Sweden.
Thomas WürdingerNeuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Rob LeursAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Marco SideriusAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Henry F VischerAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands.
Martine J SmitAmsterdam Institute for Molecules, Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1108, Amsterdam, 1081 HZ, The Netherlands. mj.smit@vu.nl.
Vrije Universiteit Amsterdam · NLAblynx (Belgium) · BEAmsterdam UMC Location Vrije Universiteit Amsterdam · NLKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) is the most aggressive and an incurable type of brain cancer. Human cytomegalovirus (HCMV) DNA and encoded proteins, including the chemokine receptor US28, have been detected in GBM tumors. US28 displays constitutive activity and is able to bind several human chemokines, leading to the activation of various proliferative and inflammatory signaling pathways. Here we show that HCMV, through the expression of US28, significantly enhanced the growth of 3D spheroids of U251- and neurospheres of primary glioblastoma cells. Moreover, US28 expression accelerated the growth of glioblastoma cells in an orthotopic intracranial GBM-model in mice. We developed highly potent and selective US28-targeting nanobodies, which bind to the extracellular domain of US28 and detect US28 in GBM tissue. The nanobodies inhibited chemokine binding and reduced the constitutive US28-mediated signaling with nanomolar potencies and significantly impaired HCMV/US28-mediated tumor growth in vitro and in vivo. This study emphasizes the oncomodulatory role of HCMV-encoded US28 and provides a potential therapeutic approach for HCMV-positive tumors using the nanobody technology.

Indexed as

AnimalsBrain NeoplasmsCell LineCell ProliferationChlorocebus aethiopsCOS CellsCytomegalovirusFemaleGlioblastomaHEK293 CellsHumansMiceMice, NudeNIH 3T3 CellsReceptors, ChemokineReceptors, VirusReceptors, ChemokineReceptors, VirusUS28 receptor, CytomegalovirusViral Proteins

Identifiers

PMID29706656
PMCPMC6062493
OpenAlexW2800241970

What OpenQuestion holds

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LicenceCC BY
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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.