Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts
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....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13996 |
| _version_ | 1811153784717443072 |
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| author | Gábor Petővári Gábor Tóth Lilla Turiák Anna L. Kiss Krisztina Pálóczi Anna Sebestyén Adrián Pesti András Kiss Kornélia Baghy Katalin Dezső Tibor Füle Péter Tátrai Ilona Kovalszky Andrea Reszegi |
| author_facet | Gábor Petővári Gábor Tóth Lilla Turiák Anna L. Kiss Krisztina Pálóczi Anna Sebestyén Adrián Pesti András Kiss Kornélia Baghy Katalin Dezső Tibor Füle Péter Tátrai Ilona Kovalszky Andrea Reszegi |
| author_sort | Gábor Petővári |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:40:12Z |
| format | Article |
| id | doaj.art-4d3f5f5114344ec0baf705f255eb0142 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:40:12Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4d3f5f5114344ec0baf705f255eb01422023-11-19T11:06:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181399610.3390/ijms241813996Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and FibroblastsGábor Petővári0Gábor Tóth1Lilla Turiák2Anna L. Kiss3Krisztina Pálóczi4Anna Sebestyén5Adrián Pesti6András Kiss7Kornélia Baghy8Katalin Dezső9Tibor Füle10Péter Tátrai11Ilona Kovalszky12Andrea Reszegi13Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryMS Proteomics Research Group, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryMS Proteomics Research Group, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok Körútja 2, H-1117 Budapest, HungaryDepartment of Human Morphology and Developmental Biology, Semmelweis University, Tűzoltó u. 58, H-1094 Budapest, HungaryDepartment of Genetics, Cell and Immunobiology, Semmelweis University, H-1085 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryThermo Fisher Scientific Inc., Váci út. 41-43, H-1134 Budapest, HungaryCharles River Laboratories Hungary, Irinyi József utca 4-20, H-1117 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryDepartment of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, HungaryTumors 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.https://www.mdpi.com/1422-0067/24/18/13996hepatoma cellfibroblasttumorstromacell communicationinvasion |
| spellingShingle | Gábor Petővári Gábor Tóth Lilla Turiák Anna L. Kiss Krisztina Pálóczi Anna Sebestyén Adrián Pesti András Kiss Kornélia Baghy Katalin Dezső Tibor Füle Péter Tátrai Ilona Kovalszky Andrea Reszegi Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts International Journal of Molecular Sciences hepatoma cell fibroblast tumor stroma cell communication invasion |
| title | Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts |
| title_full | Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts |
| title_fullStr | Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts |
| title_full_unstemmed | Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts |
| title_short | Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts |
| title_sort | dynamic interplay in tumor ecosystems communication between hepatoma cells and fibroblasts |
| topic | hepatoma cell fibroblast tumor stroma cell communication invasion |
| url | https://www.mdpi.com/1422-0067/24/18/13996 |
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