Evidence map›Paper›PMID 28581441›Full record

ArticleThe Journal of clinical investigation2017

NK cell heparanase controls tumor invasion and immune surveillance.

Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk and 3 more

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.7field-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

61 citing papers in PubMed, 98 citations in OpenAlex.

  1. Review
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  5. Dynamics of inflammatory signals within the tumor microenvironment.World journal of experimental medicine · 2025
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Eva M PutzImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Alyce J MayfoshDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Kevin KosImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Deborah S BarkauskasImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Kyohei NakamuraImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Liam TownImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Katharine J GoodallDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Dean Y YeeJohn Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
Ivan Kh PoonDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Nikola BaschukDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Fernando Souza-Fonseca-GuimaraesImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Mark D HulettDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Mark J SmythImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
La Trobe University · AUQIMR Berghofer Medical Research Institute · AUThe University of Queensland · AUAustralian National University · AU

Funding

Austrian Science Fund FWF J 3635EPA EP-C-15-008
6 · The paper itself

Abstract

NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Hpsefl/fl NKp46-iCre mice were also more susceptible to tumor growth than were their littermate controls when challenged with the established mouse lymphoma cell line RMA-S-RAE-1β, which overexpresses the NK cell group 2D (NKG2D) ligand RAE-1β, or when inoculated with metastatic melanoma, prostate carcinoma, or mammary carcinoma cell lines. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase. Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. Our data suggest that heparanase plays a critical role in NK cell invasion into tumors and thereby tumor progression and metastases. This should be considered when systemically treating cancer patients with heparanase inhibitors, since the potential adverse effect on NK cell infiltration might limit the antitumor activity of the inhibitors.

Indexed as

Immunologic SurveillanceAnimalsCell Line, TumorCytokinesFemaleHeparin LyaseHumansKiller Cells, NaturalMaleMiceMice, KnockoutNeoplasm InvasivenessNeoplasm MetastasisNeoplasms, ExperimentalNK Cell Lectin-Like Receptor Subfamily KNuclear Matrix-Associated ProteinsCytokinesHeparin LyaseKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KNuclear Matrix-Associated ProteinsNucleocytoplasmic Transport ProteinsRAE1 protein, human

Identifiers

PMID28581441
PMCPMC5490772
OpenAlexW2621095654

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.