Evidence map›Paper›PMID 39863722›Full record

ArticleScientific reports2025

Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer.

Ema Mitsui, Satoru Kikuchi, Tomohiro Okura, Hiroshi Tazawa, Yuta Une, Noriyuki Nishiwaki, Shinji Kuroda, Kazuhiro Noma, Shunsuke Kagawa, Toshiaki Ohara and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Article
  2. Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. 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

13 authors.

Ema MitsuiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Satoru KikuchiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan. satorukc@okayama-u.ac.jp.
Tomohiro OkuraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Hiroshi TazawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Yuta UneDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Noriyuki NishiwakiDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Shinji KurodaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Kazuhiro NomaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Shunsuke KagawaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Toshiaki OharaDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.
Junko OhtsukaLaboratory of Fundamental Oncology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
Rieko OhkiLaboratory of Fundamental Oncology, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.
Toshiyoshi FujiwaraDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan.

Funding

Japan Society for the Promotion of Science 24K11912
6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and α-smooth muscle (α-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with α-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and α-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC.

Indexed as

Cancer-Associated FibroblastsInterleukin-6Interleukin-6 InhibitorsPeritoneal NeoplasmsStomach NeoplasmsActinsAnimalsCell Line, TumorFemaleHumansMaleMiceMiddle AgedReceptors, Interleukin-6Tumor MicroenvironmentACTA2 protein, humanActinsIL6 protein, humanInterleukin-6Interleukin-6 InhibitorsReceptors, Interleukin-6Cancer-associated fibroblastsGastric cancerInterleukin-6Interleukin-6 receptor antibodyPeritoneal metastasis

Identifiers

PMID39863722
PMCPMC11762302

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.