Evidence map›Paper›PMID 36674635›Full record

ArticleInternational journal of molecular sciences2023

Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase.

Michio Okamoto, Rei Mizuno, Kenji Kawada, Yoshiro Itatani, Yoshiyuki Kiyasu, Keita Hanada, Wataru Hirata, Yasuyo Nishikawa, Hideyuki Masui, Naoko Sugimoto and 4 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
6.9field-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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Systematic review: The gut microbiota as a link between colorectal cancer and obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
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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

14 authors at 1 institution in 2 countries.

Michio OkamotoDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Rei MizunoDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Kenji KawadaDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.ORCID 0000-0003-4336-6937
Yoshiro ItataniDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.ORCID 0000-0001-7356-7065
Yoshiyuki KiyasuDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.ORCID 0000-0001-6527-8255
Keita HanadaDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Wataru HirataDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Yasuyo NishikawaDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Hideyuki MasuiDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Naoko SugimotoDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Takuya TamuraDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Susumu InamotoDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Yoshiharu SakaiDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Kazutaka ObamaDepartment of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.ORCID 0000-0003-2924-6701
Kyoto University · JP

Funding

Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan. 19K16771
6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase-DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.

Indexed as

Colorectal NeoplasmsExtracellular TrapsAnimalsLeukocyte ElastaseMiceMice, NudeNeoplasm Recurrence, LocalNeutrophilsLeukocyte Elastasecolorectal cancerERKneutrophil elastaseneutrophil extracellular traps

Identifiers

PMID36674635
PMCPMC9867023
OpenAlexW4313891441

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.