| Autor: |
Petővári G; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary., Tóth G; MS Proteomics Research Group, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary., Turiák L; MS Proteomics Research Group, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary., L Kiss A; Department of Human Morphology and Developmental Biology, Semmelweis University, Tűzoltó u. 58, H-1094 Budapest, Hungary., Pálóczi K; Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary., Sebestyén A; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary., Pesti A; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, Hungary., Kiss A; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, Hungary., Baghy K; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary., Dezső K; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary., Füle T; Thermo Fisher Scientific Inc., Váci út. 41-43, H-1134 Budapest, Hungary., Tátrai P; Charles River Laboratories Hungary, Irinyi József utca 4-20, H-1117 Budapest, Hungary., Kovalszky I; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary., Reszegi A; Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary.; Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, Hungary.; Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA. |
| Abstrakt: |
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. |
