ArticleCell communication and signaling : CCS2023
Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression.
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.
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12 citing papers in PubMed, 12 citations in OpenAlex.
- New insights into breast cancer therapy: application and mechanisms of novel targeted nano-formulation.International journal of pharmaceutics: X · 2026Review
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- Comparative proteomics reveals protein signatures shared between and unique to bona fide plant EVs and other plant-derived vesicles.Plant physiology · 2026Article
- Small extracellular vesicles as system-level regulators and predictive biomarkers in breast cancer progression and chemoresistance.Frontiers in pharmacology · 2026Review
- WNT5a export onto extracellular vesicles studied at single-molecule and single-vesicle resolution.The FEBS journal · 2025Article
- Syntenin Controls Extracellular Vesicle-Induced Tumour Migration by Regulating the Expression of Adhesion Proteins on Small Extracellular Vesicles.Journal of extracellular vesicles · 2025Article
- On the road: extracellular vesicles in intercellular communication.Cell communication and signaling : CCS · 2025Article
- Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.ACS nano · 2025Review
- Novel Strategies for the Treatment of Lung Cancer: An In-depth Analysis of the Use of Immunotherapy, Precision Medicine, and Artificial Intelligence to Improve Prognoses.Current medicinal chemistry · 2025Review
- G protein-coupled receptors: a gateway to targeting oncogenic EVs?Extracellular vesicles and circulating nucleic acids · 2024Review
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- Engineered Adoptive T-Cell Therapies for Breast Cancer: Current Progress, Challenges, and Potential.Cancers · 2023Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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