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THE KOREAN LIVER CANCER ASSOCIATION
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Original Article
- Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma
- Kyoungdo Mun, Jiwon Han, Pureun Roh, Jonggeun Park, Gahee Kim, Wonhee Hur, Jeongwon Jang, Jongyoung Choi, Seungkew Yoon, Youngkyoung You, Hojoong Choi, Pilsoo Sung
- J Liver Cancer. 2023;23(2):341-349. Published online June 12, 2023
- DOI: https://doi.org/10.17998/jlc.2023.04.30
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Abstract
PDF - 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. -
Citations
Citations to this article as recorded by
- Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
Siwon Mun, Hyun Jin Lee, Pilnam Kim
Experimental & Molecular Medicine.2024; 56(3): 527. CrossRef - Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC
Jong Geun Park, Pu Reun Roh, Min Woo Kang, Sung Woo Cho, Suhyun Hwangbo, Hae Deok Jung, Hyun Uk Kim, Ji Hoon Kim, Jae-Sung Yoo, Ji Won Han, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Young Kyoung You, Ho Joong Choi, Jae Yong Ryu, Pil Soo Sung
Hepatology.2024;[Epub] CrossRef
- Rebuilding the microenvironment of primary tumors in humans: a focus on stroma
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