Evidence map›Paper›PMID 31510956›Full record

ArticleBMC cancer2019

CD73 complexes with emmprin to regulate MMP-2 production from co-cultured sarcoma cells and fibroblasts.

M Aoki, K Koga, M Miyazaki, M Hamasaki, N Koshikawa, M Oyama, H Kozuka-Hata, M Seiki, B P Toole, K Nabeshima

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 29% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pantoprazole as a potential repurposed drug targeting the adenosinergic system in esophageal cancer.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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  5. The Role of Adenosine in Overcoming Resistance in Sarcomas.International journal of molecular sciences · 2024
    Review
  6. Article
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  8. Article
  9. Review
  10. Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2021
    Article
  11. CD38 in cancer-associated fibroblasts promotes pro-tumoral activity.Laboratory investigation; a journal of technical methods and pathology · 2020
    Article
  12. Article
  13. 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

10 authors at 4 institutions in 2 countries.

M AokiDepartment of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
K KogaDepartment of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
M MiyazakiDepartment of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
M HamasakiDepartment of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
N KoshikawaDivision of Cancer Cell Research, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
M OyamaMedical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
H Kozuka-HataMedical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
M SeikiDivision of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
B P TooleRegenerative Medicine & Cell Biology, Medical University of South Carolina, Charleston, USA.
K NabeshimaDepartment of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kaznabes@fukuoka-u.ac.jp.ORCID http://orcid.org/0000-0002-0691-1222
Fukuoka University · JPThe University of Tokyo · JPKanagawa Prefectural Hospital Organization · JPMedical University of South Carolina · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInteraction between cancer cells and fibroblasts mediated by extracellular matrix metalloproteinase inducer (emmprin, CD147) is important in the invasion and proliferation of cancer cells. However, the exact mechanism of emmprin mediated stimulation of matrix metalloprotease-2 (MMP-2) production from fibroblasts has not been elucidated. Our previous studies using an inhibitory peptide against emmprin suggested the presence of a molecule on the cell membrane which forms a complex with emmprin. Here we show that CD73 expressed on fibroblasts interacts with emmprin and is a required factor for MMP-2 production in co-cultures of sarcoma cells with fibroblasts.

methodsCD73 along with CD99 was identified by mass spectrometry analysis as an emmprin interacting molecule from a co-culture of cancer cells (epithelioid sarcoma cell line FU-EPS-1) and fibroblasts (immortalized fibroblasts cell line ST353i). MMP-2 production was measured by immunoblot and ELISA. The formation of complexes of CD73 with emmprin was confirmed by immunoprecipitation, and their co-localization in tumor cells and fibroblasts was shown by fluorescent immunostaining and proximity ligation assays.

resultsStimulated MMP-2 production in co-culture of cancer cells and fibroblasts was completely suppressed by siRNA knockdown of CD73, but not by CD99 knockdown. MMP-2 production was not suppressed by CD73-specific enzyme inhibitor (APCP). However, MMP-2 production was decreased by CD73 neutralizing antibodies, suggesting that CD73-mediated suppression of MMP-2 production is non-enzymatic. In human epithelioid sarcoma tissues, emmprin was immunohistochemically detected to be mainly expressed in tumor cells, and CD73 was expressed in fibroblasts and tumor cells: emmprin and CD73 were co-localized predominantly on tumor cells.

conclusionThis study provides a novel insight into the role of CD73 in emmprin-mediated regulation of MMP-2 production.

Indexed as

5'-NucleotidaseBasiginBiomarkersCell Line, TumorCoculture TechniquesFibroblastsGPI-Linked ProteinsHumansImmunohistochemistryMass SpectrometryMatrix Metalloproteinase 2Models, BiologicalProteomics5'-NucleotidaseBasiginBiomarkersBSG protein, humanGPI-Linked ProteinsMatrix Metalloproteinase 2NT5E protein, humanCD73EmmprinFibroblastsMMP-2Sarcoma

Identifiers

PMID31510956
PMCPMC6739984
OpenAlexW2972312913

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.