Evidence map›Paper›PMID 37806311›Full record

ArticleCancer science2023

M2-like tumor-associated macrophages promote epithelial-mesenchymal transition through the transforming growth factor β/Smad/zinc finger e-box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma.

Ryota Sumitomo, Toshi Menju, Yumeta Shimazu, Toshiya Toyazaki, Naohisa Chiba, Hideaki Miyamoto, Yutaka Hirayama, Shigeto Nishikawa, Satona Tanaka, Yojiro Yutaka and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.4field-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

25 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Therapeutic potential of targeting macrophage polarization in metastatic gastric cancer: a review on core mechanisms and clinical progress.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

19 authors at 3 institutions in 1 country.

Ryota SumitomoDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.ORCID https://orcid.org/0000-0002-1676-1571
Toshi MenjuDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yumeta ShimazuDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Toshiya ToyazakiDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Naohisa ChibaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hideaki MiyamotoDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yutaka HirayamaDepartment of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Shigeto NishikawaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Satona TanakaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yojiro YutakaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yoshito YamadaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Daisuke NakajimaDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Akihiro OhsumiDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Masatsugu HamajiDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Atsuyasu SatoDepartment of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Akihiko YoshizawaDepartment of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Cheng-Long HuangDepartment of Thoracic Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Hironori HagaDepartment of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Hiroshi DateDepartment of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kyoto University · JPKyoto University Hospital · JPKitano Hospital · JP

Funding

Japan Society for the Promotion of Science 20H03770
6 · The paper itself

Abstract

Epithelial-mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor-associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1-like and M2-like TAM distribution and EMT by E-cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC-1) and a human monocyte cell line (THP-1) were used for in vitro experiments. M2-like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E-cadherin-positive and 44 (19.9%) were vimentin-positive. M2-like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF-β1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF-β1 secretion from TAMs was confirmed by ELISA. TAM-co-cultured H226 and EBC-1 cells exhibited EMT (decreased E-cadherin, increased vimentin). Regarding EMT-activating transcriptional factors, phosphorylated Smad3 and ZEB-family proteins were higher in TAM-co-cultured LUSC cells than in parental cells. TAM-co-cultured H226 and EBC-1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.

Indexed as

Carcinoma, Non-Small-Cell LungCarcinoma, Squamous CellLung NeoplasmsCadherinsCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionGenes, HomeoboxHumansLungTransforming Growth Factor betaTransforming Growth Factor beta1Tumor-Associated MacrophagesVascular Endothelial Growth Factor AVimentinCadherinsTransforming Growth Factor betaTransforming Growth Factor beta1Vascular Endothelial Growth Factor AVimentinE-cadherinepithelial-mesenchymal transitionlung squamous cell carcinomatumor-associated macrophagevimentin

Identifiers

PMID37806311
PMCPMC10728010
OpenAlexW4387440985

What OpenQuestion holds

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LicenceCC BY-NC
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.