Evidence map›Paper›PMID 30941514›Full record

ArticleJournal of gastroenterology2019

Bone morphogenetic protein 4 provides cancer-supportive phenotypes to liver fibroblasts in patients with hepatocellular carcinoma.

Yohei Mano, Sachiyo Yoshio, Hirotaka Shoji, Shimagaki Tomonari, Yoshihiko Aoki, Nobuyoshi Aoyanagi, Toru Okamoto, Yoshiharu Matsuura, Yosuke Osawa, Kiminori Kimura and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  7. Metabolic Health and Disease: A Role of Osteokines?Calcified tissue international · 2023
    Review
  8. Article
  9. Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma.Cellular and molecular gastroenterology and hepatology · 2023
    Review
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  12. Article
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  16. Article
  17. Chemokine signaling in cancer-stroma communications.Journal of cell communication and signaling · 2021
    Review
  18. Review
  19. Article
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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

16 authors at 5 institutions in 1 country.

Yohei ManoThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Sachiyo YoshioThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Hirotaka ShojiThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Shimagaki TomonariThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Yoshihiko AokiThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Nobuyoshi AoyanagiDepartment of Surgery, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
Toru OkamotoDepartment of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Yoshiharu MatsuuraDepartment of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Yosuke OsawaThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.
Kiminori KimuraDepartment of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Kyohei YugawaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Huanlin WangDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshinao OdaDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomoharu YoshizumiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoshihiko MaeharaDepartment of Surgery, Kyushu Central Hospital, Fukuoka, Japan.
Tatsuya KantoThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan. kantot@hospk.ncgm.go.jp.
National Center for Global Health and Medicine · JPKyushu University · JPOsaka University · JPKyushu Central Hospital of the Mutual Aid Association of Public School Teachers · JPTokyo Metropolitan Komagome Hospital · JP

Funding

Grants-in-aid for Research from the National Center for Global Health and Medicine 26A201Instituto de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (BR) 26-shi-109the Research Program on Hepatitis from Japan Agency for Medical Research and Development 17fk0210305h0003
6 · The paper itself

Abstract

backgroundCancer-associated fibroblasts (CAFs) are essential constituents of cancer-supportive microenvironments. The high incidence of hepatocellular carcinoma (HCC) in advanced fibrosis patients implies that fibroblasts have a promoting effect on HCC development. We aimed to explore the regulators of phenotypes and function of CAFs in the liver.

methodsWe established primary cancer-associated fibroblasts (CAFs) and non-cancerous liver fibroblasts (NFs) from 15 patients who underwent HCC resection. We compared phenotypes, capacity of cytokine/chemokine production and gene expression profiles between pairs of CAFs and NFs from the same donors. We examined resected tissue from additional 50 patients with HCC for immunohistochemical analyses.

resultsThe CAFs expressed more ACTA2 and COL1A1 than the NFs, suggesting that CAFs are more activated phenotype. The CAFs produced larger amounts of IL-6, IL-8 and CCL2 than the NFs, which led to invasiveness of HuH7 in vitro. We found that Bone Morphogenetic Protein-4 (BMP4) is up-regulated in CAFs compared to NFs. The CAF phenotype and function were gained by BMP4 over-expression or recombinant BMP4 given to fibroblasts, all of which decreased with BMP4 knockdown. In tissues obtained from the patients, BMP4-positive cells are mainly observed in encapsulated fibrous lesions and HCC. Positive expression of BMP4 in HCC in resected tissues, not in fibroblasts, was associated with poorer postoperative overall survival in patients with HCC.

conclusionEndogenous and exogenous BMP4 activate liver fibroblasts to gain capacity of secreting cytokines and enhancing invasiveness of cancer cells in the liver. BMP4 is one of the regulatory factors of CAFs functioning in the microenvironment of HCC.

Indexed as

ActinsBone Morphogenetic Protein 4Carcinoma, HepatocellularCell Line, TumorCollagen Type ICollagen Type I, alpha 1 ChainCytokinesFibroblastsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLiver NeoplasmsNeoplasm InvasivenessPhenotypeRetrospective StudiesSurvival RateACTA2 protein, humanActinsBMP4 protein, humanBone Morphogenetic Protein 4Collagen Type ICollagen Type I, alpha 1 ChainCytokinesCancer-associated fibroblastsIL-6IL-8Tumor microenvironment

Identifiers

PMID30941514
OpenAlexW2925999215

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.