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Semin Liver Dis
DOI: 10.1055/a-2551-0724
Review Article

Hepatic stellate cells functional heterogeneity in liver cancer

Laura Sererols-Viñas
1   Microenvironment Plasticity and Heterogeneity Research Group, IDIBAPS, Barcelona, Spain (Ringgold ID: RIN146245)
,
Gemma Garcia-Vicién
1   Microenvironment Plasticity and Heterogeneity Research Group, IDIBAPS, Barcelona, Spain (Ringgold ID: RIN146245)
,
Paloma Ruiz-Blázquez
2   Institute of Biomedical Research of Barcelona (IIBB-CSIC), CSIC, Barcelona, Spain (Ringgold ID: RIN16379)
,
Tingfang Lee
3   Department of Surgery, Vanderbilt University Medical Center, Nashville, United States (Ringgold ID: RIN12328)
,
Youngmin Lee
3   Department of Surgery, Vanderbilt University Medical Center, Nashville, United States (Ringgold ID: RIN12328)
,
Ester Gonzalez-Sanchez
4   Department of Physiology and Pharmacology, Universidad de Salamanca, Salamanca, Spain (Ringgold ID: RIN16779)
,
Javier Vaquero
5   Centro de Investigacion del Cancer (CIC-IBMCC), CSIC, Salamanca, Spain (Ringgold ID: RIN16379)
,
Anna Moles
2   Institute of Biomedical Research of Barcelona (IIBB-CSIC), CSIC, Barcelona, Spain (Ringgold ID: RIN16379)
,
Aveline Filliol
6   Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, United States (Ringgold ID: RIN5803)
,
Silvia Affò
1   Microenvironment Plasticity and Heterogeneity Research Group, IDIBAPS, Barcelona, Spain (Ringgold ID: RIN146245)
› Author AffiliationsSupported by: Agencia Estatal de Investigación PID2021-123652OB-I00,PID2021-124694OA-I00,PID2022-141984OB-I00 ,RYC2021-034121-I,RYC2022-036321-I
Supported by: American Cancer Society RSG-22-061-01-MM
Supported by: European Research Council 101077312
Supported by: NIH 1R01DK133512
Supported by: NIH/NCI P30 CA008748
Supported by: Pfizer Foundation 77131383
› Further Information
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Hepatic stellate cells (HSCs) are the liver’s pericytes, and play key roles in liver homeostasis, regeneration, fibrosis and cancer. Upon injury, HSCs activate and are the main origin of myofibroblasts and cancer associated fibroblasts (CAFs) in liver fibrosis and cancer. Primary liver cancer has a grim prognosis, ranking as the 3rd leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the predominant type, followed by intrahepatic cholangiocarcinoma (iCCA). Moreover, the liver hosts 35% of all metastatic lesions. The distinct spatial distribution and functional roles of HSCs across these malignancies represent a significant challenge for universal therapeutic strategies, requiring a nuanced and tailored understanding of their contributions. This review examines the heterogeneous roles of HSCs in liver cancer, focusing on their spatial localization, dynamic interactions within the tumor microenvironment (TME), and emerging therapeutic opportunities, including strategies to modulate their activity, and harness their potential as targets for anti-fibrotic and anti-tumor interventions.



Publication History

Received: 12 December 2024

Accepted after revision: 04 March 2025

Accepted Manuscript online:
05 March 2025

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