Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma
Background/Aim Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. Methods Nine tumor and surrounding liver tissue samples from pat...
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| Format: | Article |
| Language: | English |
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Korean Liver Cancer Association
2023-09-01
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| Series: | Journal of Liver Cancer |
| Subjects: | |
| Online Access: | http://www.e-jlc.org/upload/pdf/jlc-2023-04-30.pdf |
| _version_ | 1797665033262465024 |
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| author | Kyoungdo Mun Jiwon Han Pureun Roh Jonggeun Park Gahee Kim Wonhee Hur Jeongwon Jang Jongyoung Choi Seungkew Yoon Youngkyoung You Hojoong Choi Pilsoo Sung |
| author_facet | Kyoungdo Mun Jiwon Han Pureun Roh Jonggeun Park Gahee Kim Wonhee Hur Jeongwon Jang Jongyoung Choi Seungkew Yoon Youngkyoung You Hojoong Choi Pilsoo Sung |
| author_sort | Kyoungdo Mun |
| collection | DOAJ |
| description | Background/Aim Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. Methods Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay. Results CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2. Conclusions CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis. |
| first_indexed | 2024-03-11T19:38:03Z |
| format | Article |
| id | doaj.art-e059b138163241bf9d6c05a9c799a24f |
| institution | Directory Open Access Journal |
| issn | 2288-8128 2383-5001 |
| language | English |
| last_indexed | 2024-03-11T19:38:03Z |
| publishDate | 2023-09-01 |
| publisher | Korean Liver Cancer Association |
| record_format | Article |
| series | Journal of Liver Cancer |
| spelling | doaj.art-e059b138163241bf9d6c05a9c799a24f2023-10-06T13:06:50ZengKorean Liver Cancer AssociationJournal of Liver Cancer2288-81282383-50012023-09-0123234134910.17998/jlc.2023.04.30529Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinomaKyoungdo Mun0Jiwon Han1Pureun Roh2Jonggeun Park3Gahee Kim4Wonhee Hur5Jeongwon Jang6Jongyoung Choi7Seungkew Yoon8Youngkyoung You9Hojoong Choi10Pilsoo Sung11 The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, Cheongju, Korea Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, Cheongju, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, Korea Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea The Catholic University Liver Research Center and POSTECH-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University Korea, Seoul, KoreaBackground/Aim Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. Methods Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay. Results CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2. Conclusions CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.http://www.e-jlc.org/upload/pdf/jlc-2023-04-30.pdfcarcinoma, hepatocellularcancer-associated fibroblaststumor microenvironmentcytokines |
| spellingShingle | Kyoungdo Mun Jiwon Han Pureun Roh Jonggeun Park Gahee Kim Wonhee Hur Jeongwon Jang Jongyoung Choi Seungkew Yoon Youngkyoung You Hojoong Choi Pilsoo Sung Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma Journal of Liver Cancer carcinoma, hepatocellular cancer-associated fibroblasts tumor microenvironment cytokines |
| title | Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| title_full | Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| title_fullStr | Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| title_full_unstemmed | Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| title_short | Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| title_sort | isolation and characterization of cancer associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma |
| topic | carcinoma, hepatocellular cancer-associated fibroblasts tumor microenvironment cytokines |
| url | http://www.e-jlc.org/upload/pdf/jlc-2023-04-30.pdf |
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