Friend or foe? The elusive role of hepatic stellate cells in liver cancer.
Journal
Nature reviews. Gastroenterology & hepatology
ISSN: 1759-5053
Titre abrégé: Nat Rev Gastroenterol Hepatol
Pays: England
ID NLM: 101500079
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
accepted:
06
07
2023
pmc-release:
01
04
2024
medline:
22
9
2023
pubmed:
8
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
Liver fibrosis is a substantial risk factor for the development and progression of liver cancer, which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Studies utilizing cell fate mapping and single-cell transcriptomics techniques have identified quiescent perisinusoidal hepatic stellate cells (HSCs) as the primary source of activated collagen-producing HSCs and liver cancer-associated fibroblasts (CAFs) in HCC and liver metastasis, complemented in iCCA by contributions from portal fibroblasts. At the same time, integrative computational analysis of single-cell, single-nucleus and spatial RNA sequencing data have revealed marked heterogeneity among HSCs and CAFs, with distinct subpopulations displaying unique gene expression signatures and functions. Some of these subpopulations have divergent roles in promoting or inhibiting liver fibrogenesis and carcinogenesis. In this Review, we discuss the dual roles of HSC subpopulations in liver fibrogenesis and their contribution to liver cancer promotion, progression and metastasis. We review the transcriptomic and functional similarities between HSC and CAF subpopulations, highlighting the pathways that either promote or prevent fibrosis and cancer, and the immunological landscape from which these pathways emerge. Insights from ongoing studies will yield novel strategies for developing biomarkers, assessing prognosis and generating new therapies for both HCC and iCCA prevention and treatment.
Identifiants
pubmed: 37550577
doi: 10.1038/s41575-023-00821-z
pii: 10.1038/s41575-023-00821-z
pmc: PMC10671228
mid: NIHMS1943184
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
647-661Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK128289
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078207
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121154
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007280
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK136016
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
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