Evidence map›Paper›PMID 36683050›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

Mesothelioma-associated fibroblasts enhance proliferation and migration of pleural mesothelioma cells via c-Met/PI3K and WNT signaling but do not protect against cisplatin.

Alexander Ries, Daniela Flehberger, Astrid Slany, Christine Pirker, Johanna C Mader, Thomas Mohr, Karin Schelch, Katharina Sinn, Berta Mosleh, Mir Alireza Hoda and 7 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 19 citations in OpenAlex.

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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

17 authors at 5 institutions in 3 countries.

Alexander RiesCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Daniela FlehbergerCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Astrid SlanyDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090, Vienna, Austria.
Christine PirkerCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Johanna C MaderDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090, Vienna, Austria.
Thomas MohrCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Karin SchelchCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Katharina SinnDepartment of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
Berta MoslehDepartment of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
Mir Alireza HodaDepartment of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
Balazs DomeDepartment of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.
Helmut DolznigInstitute of Medical Genetics, Medical University of Vienna, Waehringer Straße 10, 1090, Vienna, Austria.
Georg KrupitzaDepartment of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Leonhard MüllauerDepartment of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Christopher GernerDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090, Vienna, Austria.
Walter BergerCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.
Michael GruschCenter for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria. michael.grusch@meduniwien.ac.at.
Medical University of Vienna · ATComprehensive Cancer Center Vienna · ATUniversity of Vienna · ATSemmelweis University · HUThomas University · US

Funding

Austrian Science Fund FWF I 3522Austrian Science Fund FWF I 3977Austrian Science Fund FWF I 4677Austrian Science Fund FWF T 1062
6 · The paper itself

Abstract

backgroundPleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, PM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several malignancies. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on PM cells.

methodsMeso-CAFs were isolated from surgical specimens of PM patients and analyzed by array comparative genomic hybridization, next generation sequencing, transcriptomics and proteomics. Human PM cell lines were retrovirally transduced with GFP. The impact of Meso-CAFs on tumor cell growth, migration, as well as the response to small molecule inhibitors, cisplatin and pemetrexed treatment was investigated in 2D and 3D co-culture models by videomicroscopy and automated image analysis.

resultsMeso-CAFs show a normal diploid genotype without gene copy number aberrations typical for PM cells. They express CAF markers and lack PM marker expression. Their proteome and secretome profiles clearly differ from normal lung fibroblasts with particularly strong differences in actively secreted proteins. The presence of Meso-CAFs in co-culture resulted in significantly increased proliferation and migration of PM cells. A similar effect on PM cell growth and migration was induced by Meso-CAF-conditioned medium. Inhibition of c-Met with crizotinib, PI3K with LY-2940002 or WNT signaling with WNT-C59 significantly impaired the Meso-CAF-mediated growth stimulation of PM cells in co-culture at concentrations not affecting the PM cells alone. Meso-CAFs did not provide protection of PM cells against cisplatin but showed significant protection against the EGFR inhibitor erlotinib.

conclusionsOur study provides the first characterization of human patient-derived Meso-CAFs and demonstrates a strong impact of Meso-CAFs on PM cell growth and migration, two key characteristics of PM aggressiveness, indicating a major role of Meso-CAFs in driving PM progression. Moreover, we identify signaling pathways required for Meso-CAF-mediated growth stimulation. These data could be relevant for novel therapeutic strategies against PM.

Indexed as

MesotheliomaMesothelioma, MalignantCell Line, TumorCell ProliferationCisplatinComparative Genomic HybridizationFibroblastsHumansPhosphatidylinositol 3-KinasesTumor MicroenvironmentWnt Signaling PathwayCisplatinPhosphatidylinositol 3-KinasesCancer-associated fibroblastsCisplatinC-MetCo-culturesHGFPemetrexedPI3KPleural mesotheliomaTumor microenvironmentWNT

Identifiers

PMID36683050
PMCPMC9869633
OpenAlexW4317715926

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.