Tumor-matrix interaction induces phenotypic switching in liver cancer cells.
Cholangiocarcinoma
Extracellular matrix
Hepatocellular carcinoma
Invasion
Mitogen-activated protein kinase
Journal
Hepatology international
ISSN: 1936-0541
Titre abrégé: Hepatol Int
Pays: United States
ID NLM: 101304009
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
06
11
2021
accepted:
13
02
2022
pubmed:
8
5
2022
medline:
10
6
2022
entrez:
7
5
2022
Statut:
ppublish
Résumé
Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix. Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA sequencing showed that in the liver cancer cells, collagen 1 upregulated cell cycle inhibitor expression and cell-matrix interaction, tumor migration, and angiogenesis pathways, but downregulated liver metabolic function pathways. Cholangiocytic differentiation and invasiveness induced by collagen 1 was mediated by the mitogen-activated protein kinase (MAPK) pathway, which was regulated by cell-matrix interaction-induced Src activation. Analysis of the Cancer Genome Atlas cohort showed that collagen 1 induced and suppressed genes were highly enriched in ICC and HCC, respectively. In HCC samples, collagen 1-regulated genes were strongly coexpressed and correlated with COL1A1 expression. Liver cancer cell-matrix interaction induces cholangiocytic differentiation and switches liver cancer cells from a proliferative to an invasive phenotype through the Src/MAPK pathway, which may partly explain the differences in the behaviors of HCC and ICC.
Sections du résumé
BACKGROUND
BACKGROUND
Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix.
METHODS AND RESULTS
RESULTS
Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA sequencing showed that in the liver cancer cells, collagen 1 upregulated cell cycle inhibitor expression and cell-matrix interaction, tumor migration, and angiogenesis pathways, but downregulated liver metabolic function pathways. Cholangiocytic differentiation and invasiveness induced by collagen 1 was mediated by the mitogen-activated protein kinase (MAPK) pathway, which was regulated by cell-matrix interaction-induced Src activation. Analysis of the Cancer Genome Atlas cohort showed that collagen 1 induced and suppressed genes were highly enriched in ICC and HCC, respectively. In HCC samples, collagen 1-regulated genes were strongly coexpressed and correlated with COL1A1 expression.
CONCLUSIONS
CONCLUSIONS
Liver cancer cell-matrix interaction induces cholangiocytic differentiation and switches liver cancer cells from a proliferative to an invasive phenotype through the Src/MAPK pathway, which may partly explain the differences in the behaviors of HCC and ICC.
Identifiants
pubmed: 35525880
doi: 10.1007/s12072-022-10315-w
pii: 10.1007/s12072-022-10315-w
doi:
Substances chimiques
Collagen
9007-34-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-576Subventions
Organisme : Ministry of Science and Technology, Republic of China
ID : 108-2320-B-002 -059 -MY3
Organisme : Ministry of Science and Technology, Republic of China
ID : 109-2314-B-002 -082 -
Informations de copyright
© 2022. Asian Pacific Association for the Study of the Liver.
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