PUBLICATION
A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism
- Authors
- Basol, M., Korhan, P., Ozaktas, H., Atabey, N., Cakan-Akdogan, G.
- ID
- ZDB-PUB-260307-8
- Date
- 2026
- Source
- Liver international : official journal of the International Association for the Study of the Liver 46: e70579e70579 (Journal)
- Registered Authors
- Cakan-Akdogan, Gülcin, Özaktaş, Helin
- Keywords
- CTC model, IV injection, hepatocellular carcinoma, liver‐specific metastasis, zLiverMet, zebrafish
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Colorectal Neoplasms*/pathology
- Disease Models, Animal
- Humans
- Liver/pathology
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Liver Neoplasms*/secondary
- Proto-Oncogene Proteins c-met*/antagonists & inhibitors
- Proto-Oncogene Proteins c-met*/genetics
- Proto-Oncogene Proteins c-met*/metabolism
- Zebrafish
- PubMed
- 41788023 Full text @ Liver Int.
Citation
Basol, M., Korhan, P., Ozaktas, H., Atabey, N., Cakan-Akdogan, G. (2026) A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism. Liver international : official journal of the International Association for the Study of the Liver. 46:e70579e70579.
Abstract
Background and aims Intrahepatic metastasis negatively impacts the prognosis of several cancers, including hepatocellular and colorectal carcinoma. Zebrafish larval xenografts serve as a robust vertebrate platform that allows direct visualisation of tumour behaviour within a living organism. However, organ-specific metastasis models in zebrafish remain limited, and liver metastasis has not yet been demonstrated. This study aimed to establish a zebrafish larval intrahepatic metastasis model and to determine the role of c-Met activation in mediating liver tropism of cancer cells.
Methods An intravenous injection-based zebrafish model (zLiverMet) was developed using a liver-specific fluorescent reporter line to visualise tumour colonisation in vivo. Liver cancer cell lines with distinct c-Met expression and activation levels were injected into 2-day post-fertilisation larvae. The effects of c-Met overexpression and pharmacological inhibition on intrahepatic metastasis were analysed through confocal imaging and quantitative image measurements. The model's applicability was further tested using colorectal cancer (CRC) cell lines.
Results Intravenous injection facilitated efficient intrahepatic colonisation, whereas yolk-sac injection failed to reproduce vascular dissemination. Liver cancer cell lines with high c-Met expression, SNU-449, Mahlavu and SK-HEP-1, exhibited strong liver tropism, while cell lines with no/low c-Met expression, HuH-7 and SNU-398, showed minimal hepatic metastasis. Overexpressing c-Met increased liver colonisation of HCC cells, and inhibiting c-Met activation with the c-Met inhibitor SU11274 reduced this effect.
Conclusions The zLiverMet model successfully mimics intrahepatic metastasis and highlights c-Met as a driver of liver tropism. This zebrafish-based model offers an 'organism-on-a-chip' platform that is rapid, imageable and scalable-bridging in vitro assays and in vivo models for mechanistic and therapeutic studies of liver metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping