ArticleInternational journal of molecular sciences2023
Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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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
11 citing papers in PubMed, 14 citations in OpenAlex.
- The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- Distinct Proteomic and Glycosylation Signatures Differentiate A549 Tumor and BEAS-2B Nontumor Cell Line-Derived Small Extracellular Vesicles.Molecular & cellular proteomics : MCP · 2026Article
- The role of thrombospondin-1 in dermatological conditions.Frontiers in medicine · 2026Review
- Extracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis.ACS nano · 2025Review
- Unraveling the Role of the Wnt Pathway in Hepatocellular Carcinoma: From Molecular Mechanisms to Therapeutic Implications.Journal of clinical and translational hepatology · 2025Review
- Multidimensional insights into exosomes in hepatocellular carcinoma: from genesis to clinical application.Frontiers in immunology · 2025Review
- Prospect of extracellular vesicles in tumor immunotherapy.Frontiers in immunology · 2025Review
- Current trends in theranostic applications of extracellular vesicles in cancer.Frontiers in oncology · 2025Review
- Organotropic metastasis in colorectal cancer: integrating molecular pathways with therapeutic opportunities.Frontiers in immunology · 2025Review
- Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.Cell & bioscience · 2024Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumors are intricate ecosystems where cancer cells and non-malignant stromal cells, including cancer-associated fibroblasts (CAFs), engage in complex communication. In this study, we investigated the interaction between poorly (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts. We explored various communication channels, including soluble factors, metabolites, extracellular vesicles (EVs), and miRNAs. Co-culture with HLE cells induced LX2 to produce higher levels of laminin β1, type IV collagen, and CD44, with pronounced syndecan-1 shedding. Conversely, in HuH7/LX2 co-culture, fibronectin, thrombospondin-1, type IV collagen, and cell surface syndecan-1 were dominant matrix components. Integrins α6β4 and α6β1 were upregulated in HLE, while α5β1 and αVβ1 were increased in HuH7. HLE-stimulated LX2 produced excess MMP-2 and 9, whereas HuH7-stimulated LX2 produced excess MMP-1. LX2 activated MAPK and Wnt signaling in hepatoma cells, and conversely, hepatoma-derived EVs upregulated MAPK and Wnt in LX2 cells. LX2-derived EVs induced over tenfold upregulation of SPOCK1/testican-1 in hepatoma EV cargo. We also identified liver cancer-specific miRNAs in hepatoma EVs, with potential implications for early diagnosis. In summary, our study reveals tumor type-dependent communication between hepatoma cells and fibroblasts, shedding light on potential implications for tumor progression. However, the clinical relevance of liver cancer-specific miRNAs requires further investigation.
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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.