Senescent hepatic stellate cells caused by deoxycholic acid modulates malignant behavior of hepatocellular carcinoma.
Antibodies, Neutralizing
/ pharmacology
Carcinoma, Hepatocellular
/ genetics
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cellular Senescence
/ drug effects
Deoxycholic Acid
/ pharmacology
Epithelial-Mesenchymal Transition
/ drug effects
Hepatic Stellate Cells
/ drug effects
Humans
Interleukin-8
/ antagonists & inhibitors
Liver
/ drug effects
Liver Neoplasms
/ genetics
Signal Transduction
/ drug effects
Transforming Growth Factor beta
/ antagonists & inhibitors
Cellular senescence
Deoxycholic acid
Epithelial mesenchymal transition
Hepatic stellate cells
Hepatocellular carcinoma
Senescence-associated secretory phenotype
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
11
06
2020
accepted:
21
08
2020
pubmed:
2
9
2020
medline:
15
12
2020
entrez:
2
9
2020
Statut:
ppublish
Résumé
Deoxycholic acid (DCA), a secondary bile acid, is reportedly increased in the serum of patients with nonalcoholic steatohepatitis and animals with experimentally induced hepatocellular carcinoma (HCC), but its contribution to malignant behaviors of HCC has not been precisely clarified. This study aimed to examine the effect of DCA on hepatic stellate cells (HSCs), a major component of nonparenchymal cells in the liver, and its subsequent indirect effect on HCC cells. LX2 cells, a human HSC line, were treated with DCA in vitro. Then, HuH7 cells, a human hepatoma cell line, were incubated in conditioned media of DCA-treated LX2 to investigate the subsequent effect focusing on malignant behaviors. DCA resulted in cellular senescence in LX2 with the decreased cell proliferation via cell cycle arrest at G0/1 phase, together with the induction of senescence-associated secretory phenotype (SASP) factors. To investigate the influence of SASP factors secreted by HSCs in response to DCA, HCC cells were treated with conditioned media that promoted cell migration and invasion via induction of epithelial mesenchymal transition. These changes were attenuated in the presence of neutralizing antibody against IL8 or TGFβ. Pathological analysis of surgical specimens from HCC patients revealed that senescent HSCs were detected in the stroma surrounding HCC. Our data suggest an important role of HSC senescence caused by DCA for the malignant biological behaviors of HCC via induction of SASP factors, particularly IL8 and TGFβ.
Identifiants
pubmed: 32870388
doi: 10.1007/s00432-020-03374-9
pii: 10.1007/s00432-020-03374-9
doi:
Substances chimiques
Antibodies, Neutralizing
0
Interleukin-8
0
Transforming Growth Factor beta
0
Deoxycholic Acid
005990WHZZ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3255-3268Subventions
Organisme : Japan Society for the Promotion of Science
ID : 19K18963
Organisme : Japan Society for the Promotion of Science
ID : 18K07940
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