Evidence map›Paper›PMID 37430307›Full record

ArticleCell communication and signaling : CCS2023

Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression.

Barnabas Irmer, Janes Efing, Lea Elisabeth Reitnauer, Allegra Angenendt, Saskia Heinrichs, Antonia Schubert, Matthias Schulz, Claudia Binder, Joke Tio, Uwe Hansen and 4 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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  5. Article
  6. Article
  7. On the road: extracellular vesicles in intercellular communication.Cell communication and signaling : CCS · 2025
    Article
  8. Review
  9. Review
  10. G protein-coupled receptors: a gateway to targeting oncogenic EVs?Extracellular vesicles and circulating nucleic acids · 2024
    Review
  11. Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024
    Review
  12. 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

14 authors at 4 institutions in 1 country.

Barnabas Irmer *University Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Janes Efing *University Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Lea Elisabeth ReitnauerUniversity Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Allegra AngenendtUniversity Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Saskia HeinrichsUniversity Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Antonia SchubertDivision Signaling and Functional Genomics, German Cancer Research Center (DKFZ) and Heidelberg University, Heidelberg, Germany.
Matthias SchulzDept. of Hematology/Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
Claudia BinderDept. of Hematology/Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
Joke TioDept. of Obstetrics and Gynaecology, University of Münster, Münster, Germany.
Uwe HansenInstitute for Musculoskeletal Medicine, University of Münster, Münster, Germany.
Christiane GeyerClinic for Radiology, University of Münster, Münster, Germany.
Mirjam GerwingClinic for Radiology, University of Münster, Münster, Germany.
Annalen BleckmannUniversity Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany.
Kerstin MenckUniversity Hospital Münster, Dept. of Medicine A, Albert-Schweitzer-Campus 1 D3, 48149, Münster, Germany. kerstin.menck@ukmuenster.de.
University Hospital Münster · DEUniversitätsmedizin Göttingen · DEUniversity of Münster · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExtracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression.

methodsEVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays.

resultsWe observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls.

conclusionsThe oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression. Video Abstract.

Indexed as

Extracellular VesiclesSkin NeoplasmsAnimalsCutaneous Malignant MelanomaMiceProtein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsTissue DistributionTumor MicroenvironmentProtein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsRor1 protein, mouseRor2 protein, mouse

Identifiers

PMID37430307
PMCPMC10331971
OpenAlexW4383722144

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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.