Evidence map›Paper›PMID 29016864›Full record

ArticleNeuro-oncology2018

Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment.

Frank Szulzewsky, Nina Schwendinger, Dilansu Güneykaya, Patrick J Cimino, Dolores Hambardzumyan, Michael Synowitz, Eric C Holland, Helmut Kettenmann

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. The Landscape of SPP1Immunology · 2025
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  11. Article
  12. Review
  13. Article
  14. Macrophages and microglia: the cerberus of glioblastoma.Acta neuropathologica communications · 2021
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors at 4 institutions in 2 countries.

Frank SzulzewskyCellular Neurosciences, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association and Berlin Institute of Health, Berlin, Germany.
Nina SchwendingerCellular Neurosciences, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association and Berlin Institute of Health, Berlin, Germany.
Dilansu GüneykayaCellular Neurosciences, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association and Berlin Institute of Health, Berlin, Germany.
Patrick J CiminoDepartment of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Dolores HambardzumyanDepartment of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
Michael SynowitzDepartment of Neurosurgery, University Medical Center Schleswig-Holstein, Kiel, Germany.
Eric C HollandDepartment of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Helmut KettenmannCellular Neurosciences, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association and Berlin Institute of Health, Berlin, Germany.
Fred Hutch Cancer Center · USMax Delbrück Center · DEAflac (United States) · USUniversity of Lübeck · DE

Funding

NIH HHS U01CA160882-01A1
6 · The paper itself

Abstract

Background: Microglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing, we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1. Methods: We used quantitative reverse transcriptase PCR, immunofluorescence stainings, western blot, and flow cytometry to identify the various sources of osteopontin (OPN) expression in human and mouse glioblastoma. We implanted wild type GL261 glioblastoma cells, which do not express significant levels of OPN, into wild type and OPN-/- mice to investigate the role of microenvironment-derived OPN on glioblastoma progression. Results: Our data indicate that GAMs are the predominant source of OPN in both human and mouse glioblastoma and express only the secreted form of OPN. Loss of microenvironment-derived OPN enhanced tumor progression. Staining by Ki67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling showed no difference in overall cell proliferation but a decreased apoptosis rate in tumors in OPN-/- mice. CD31 staining showed a significantly decreased number of microvessels in tumors in OPN-/- mice, accompanied by reduced coverage of vessels with platelet derived growth factor receptor β+ pericytes. Flow cytometry analysis revealed a significant increase of CD11b+/CD45low microglia but not of CD11b+/CD45high macrophages/monocytes in tumors in OPN-/- mice. Sorted CD11b+ cells from wild type and OPN-/- naïve brains and tumors did not show a significant difference in the expression pattern of activation marker genes. Conclusion: Our results show that in tested human and mouse glioblastoma samples, OPN is predominantly expressed and secreted by GAMs and that, in contrast to OPN expression in the tumor cells per se, loss of stroma-derived OPN creates a glioblastoma-promoting microenvironment.

Indexed as

Tumor MicroenvironmentAnimalsApoptosisBrain NeoplasmsCell MovementCell ProliferationDisease ProgressionGlioblastomaHumansMiceMice, Inbred C57BLMicrogliaMonocytesOsteopontinOsteopontin

Identifiers

PMID29016864
PMCPMC5817947
OpenAlexW2750179473

What OpenQuestion holds

Textmetadata
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.