ArticleCancer science2019
Exosomes containing ErbB2/CRK induce vascular growth in premetastatic niches and promote metastasis of bladder cancer.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- Before the seeds arrive: pre-metastatic niche orchestration in bladder cancer.Cancer metastasis reviews · 2026Review
- Tumoral extracellular vesicles and particles reprogram interstitial macrophages in the lung to promote vascular permeability and metastasis.Nature cancer · 2026Article
- Exosomal nanocarriers of immune fate: molecular insights into cancer immunity, pathogen defense, and emerging immunotherapies.Clinical and experimental immunology · 2026Review
- Breaking the premetastatic niche barrier: the role of endothelial cells and therapeutic strategies.Theranostics · 2025Review
- Extracellular vesicles-a new player in the development of urinary bladder cancer.Therapeutic advances in medical oncology · 2025Review
- Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.European journal of medical research · 2024Review
- Blockade of Crk eliminates Yki/YAP-activated tumors via JNK-mediated apoptosis in Drosophila.Communications biology · 2024Article
- Tumour-derived Extracellular Vesicle and Particle Reprogramming of Interstitial Macrophages in the Lung Pre-Metastatic Niche Enhances Vascular Permeability and Metastatic Potential.Research square · 2024Article
- Exosomal Proteomics: Unveiling Novel Insights into Lung Cancer.Aging and disease · 2024Review
- Alternative splicing regulation and its therapeutic potential in bladder cancer.Frontiers in oncology · 2024Review
- Cellular and molecular characteristics of the premetastatic niches.Animal models and experimental medicine · 2023Review
- Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors.Cells · 2023Article
- Blood-based liquid biopsy: insights into early detection, prediction, and treatment monitoring of bladder cancer.Cellular & molecular biology letters · 2023Review
- Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells.Molecular oncology · 2023Article
- Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma.Frontiers in medicine · 2023Review
- Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via Targeting SIRT1.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Extracellular vesicles and particles impact the systemic landscape of cancer.The EMBO journal · 2022Review
- Emerging role of exosomes in cancer progression and tumor microenvironment remodeling.Journal of hematology & oncology · 2022Review
- Anti-Metastatic Function of Extracellular Vesicles Derived fromCurrent oncology (Toronto, Ont.) · 2022Article
- Prediction of Prognosis and Recurrence of Bladder Cancer by ECM-Related Genes.Journal of immunology research · 2022Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Locally advanced and metastatic invasive bladder cancer (BC) has a poor prognosis, and no advanced therapies beyond cisplatin-based combination chemotherapy have been developed. Therefore, it is an urgent issue to elucidate the underlying mechanisms of tumor progression and metastasis of invasive BC for the development of new therapeutic strategies. Here, we clarified a novel role of exosomes containing ErbB2 and CRK in a formation of premetastatic niches and subsequent metastases. CRK adaptors were overexpressed in invasive UM-UC-3 BC cells. In an orthotopic xenograft model, metastases to lung, liver, and bone of UM-UC-3 cells were completely abolished by CRK elimination. Mass spectrometry analysis identified that ErbB2 was contained in UM-UC-3-derived exosomes in a CRK-dependent manner; the exosomes significantly increased proliferation and invasion properties of low-grade 5637 BC cells and HUVECs through FAK and PI3K/AKT signaling pathways. In athymic mice educated with UM-UC-3-derived exosomes, i.v. implanted UM-UC-3 cells were trapped with surrounding PKH67-labeled exosomes in lung and led to development of lung metastasis with disordered vascular proliferation. In contrast, exosomes derived from CRK-depleted BC cells failed to induce these malignant features. Taken together, we showed that CRK adaptors elevated the expression of ErbB2/3 in BC cells, and these tyrosine kinase/adaptor units were transferred from host BC cells to metastatic recipient cells by exosomes, leading to vascular leakiness and proliferation and contributing to the formation of distant metastasis. Thus, CRK intervention with ErbB2/3 blockade might be a potent therapeutic strategy for patients with ErbB2 overexpressing advanced and metastatic BC.
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Registered trials
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