ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Large Oncosome-Loaded VAPA Promotes Bone-Tropic Metastasis of Hepatocellular Carcinoma Via Formation of Osteoclastic Pre-Metastatic Niche.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Extracellular Vesicles as Nanoparticle Delivery Vectors in Cancer Therapy.Nano letters · 2026Review
- Use of the J774A.1 Cell Line as a Model in the In Vitro Study of Extracellular Vesicle Secretion from Histiocytic Sarcoma in Patients with Bacterial Co-Infections.International journal of molecular sciences · 2026Article
- The Osteoblastic Microenvironment Determines the Fate of Breast Cancer Cells Disseminated in the Bone Marrow.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Contribution of tumor-derived extracellular vesicles in the establishment of the pre-metastatic niche: lessons learned from past experimentations and future directions.Clinical & experimental metastasis · 2026Review
- Review
- Large extracellular vesicles and blebbisomes in cancer: emerging and translational opportunities highlights.Cell communication and signaling : CCS · 2026Review
- Bacterial Extracellular Vesicles in Aging: Mechanisms and Therapeutic Prospects.International journal of nanomedicine · 2026Review
- Extracellular vesicle heterogeneity through the lens of multiomics.Cell reports. Medicine · 2025Article
- Macrophages in the premetastatic and metastatic niche: key functions and therapeutic directions.Journal of translational medicine · 2025Review
- Transcriptomic profiling of circulating tumor cells from metastatic breast cancer patients reveals new hints in their biological features and phenotypic heterogeneity.Experimental hematology & oncology · 2025Article
- Extracellular particles: emerging insights into central nervous system diseases.Journal of nanobiotechnology · 2025Review
- Regulation of metastatic organotropism.Trends in cancer · 2025Review
- Functional hydrogel empowering 3D printing titanium alloys.Materials today. Bio · 2025Review
- Study on molecular mechanism of intervertebral disc degeneration by single cell hdWGCNA combined with transcriptome sequencing.Non-coding RNA research · 2025Article
- Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential.World journal of hepatology · 2024Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.Cell & bioscience · 2024Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Tumor-derived extracellular vesicles (EVs) function as critical mediators in selective modulation of the microenvironment of distant organs to generate a pre-metastatic niche that facilitates organotropic metastasis. Identifying the organ-specific molecular determinants of EVs can develop potential anti-metastatic therapeutic targets. In the current study, large oncosomes (LOs), atypically large cancer-derived EVs, are found to play a crucial role in facilitating bone-tropic metastasis of hepatocellular carcinoma (HCC) cells by engineering an osteoclastic pre-metastatic niche and establishing a vicious cycle between the osteoclasts and HCC cells. Transmembrane protein, VAMP-associated protein A (VAPA), is significantly enriched on LOs surface via direct interaction with LOs marker αV-integrin. VAPA-enriched LOs-induced pre-metastatic education transforms the bone into a fertile milieu, which supports the growth of metastatic HCC cells. Mechanically, LOs-delivered VAPA integrates to plasma membrane of osteoclasts and directly interacts with and activates neural Wiskott-Aldrich syndrome protein (N-WASP) via dual mechanisms, consequently resulting in ARP2/3 complex-mediated reorganization of actin cytoskeleton in osteoclasts and osteoclastogenesis. Importantly, treatment with N-WASP inhibitor 187-1-packaged LOs (LOs/187-1) dramatically abolishes the inductive effect of VAPA-enriched LOs on pre-metastatic niche formation and precludes HCC bone metastasis. These findings reveal a plausible mechanism for bone-tropism of HCC and can represent a potential strategy to prevent HCC bone metastasis.
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Registered trials
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.