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This study established a zebrafish larval intrahepatic metastasis model (zLiverMet) and assessed how c-Met activation regulates liver tropism of cancer cells. Zebrafish larvae received intravenous tumor-cell injections using a liver-specific fluorescent reporter to visualize colonisation in vivo. Confocal imaging and quantitative measurements evaluated c-Met overexpression and SU11274 inhibition, with validation in colorectal cancer cells.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-novel-zebrafish-liver-specific-metastasis-model-reveals-c-met-as-a-driver-of-liver-tropism/352525/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-novel-zebrafish-liver-specific-metastasis-model-reveals-c-met-as-a-driver-of-liver-tropism/352525.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-26","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the zLiverMet model and what does it measure?","Question",{"text":112,"@type":113},"zLiverMet is a zebrafish larval intravenous-injection model built with a liver-specific fluorescent reporter to visualize and quantify tumour colonisation in the liver in vivo.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why does the study focus on c-Met in liver tropism?",{"text":117,"@type":113},"The research tests whether c-Met activation drives the ability of cancer cells to preferentially colonise the liver, using cells with different c-Met expression/activation states and pharmacological inhibition.",{"name":119,"@type":110,"acceptedAnswer":120},"How did SU11274 affect intrahepatic metastasis in the model?",{"text":121,"@type":113},"Inhibiting c-Met activation with SU11274 reduced intrahepatic liver colonisation induced by c-Met overexpression, indicating a functional role for c-Met signaling in liver tropism.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},352525,1790404132,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","Liver International  \nORIGINAL ARTICLE  OPEN ACCESS   \nA Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism  \nMerve Basol1,2  | Peyda Korhan1,3,4  | Helin Ozaktas1,2  | Nese Atabey1,3,4  | Gulcin Cakan-Akdogan1,2   \n1Izmir Biomedicine and Genome Center, Izmir, Türkiye | 2Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Türkiye | 3Galen Research Center, Izmir Tinaztepe University, Izmir, Türkiye | 4Department of Medical Biology, Faculty of Medicine, Izmir Tinaztepe University, Izmir, Türkiye  \nCorrespondence: Nese Atabey ([nese.atabey@ibg.edu.tr](nese.atabey@ibg.edu.tr)) | Gulcin Cakan-Akdogan ([gulcin.cakan@ibg.edu.tr](gulcin.cakan@ibg.edu.tr))  \nReceived: 29 October 2025 | Revised: 9 January 2026 | Accepted: 16 February 2026  \nHandling Editor: Luca Valenti  \nKeywords: CTC model | hepatocellular carcinoma | IV injection | liver-specific metastasis | zebrafish | zLiverMet  \nABSTRACT  \nBackground 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.  \nMethods: 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.  \nResults: 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.  \n1 | Introduction  \nMore than 90% of the cancer-related mortalities are attributable to tumour invasion and metastasis [1, 2] . The liver is one of the most common metastatic targets for various cancer types,  \nincluding hepatocellular carcinoma (HCC) and colorectal cancer (CRC) [2, 3] . Intrahepatic metastases significantly worsen the survival of patients [4–8] . Cancer cells that complete the metastasis cascade can induce secondary tumours. This multistep process begins with the local invasion of malignant  \n\n| Abbreviations: AC, adenocarcinoma; c-Met, c-mesenchymal-epithelial transition factor; cmlc2 , cardiac myosin light chain 2; CRC, colorectal cancer cell; CTCs, circulating tumour cells; dpf, day post fertilisation; ECM, extracellular matrix; fabp10a, fatty acid binding protein 10 a; HCC, hepatocellular carcinoma; HGF, hepatocyte growth factor; IV, intravenous injection; OE, overexpression; p-c-Met, phospho-c-Met; p-MAPK, phospho-MAPK. |\n| --- |\n| This is an open access article under the terms of the","cbCaivlwIkqu3yxi","https://ap.wps.com/l/cbCaivlwIkqu3yxi","pdf",5484143,12,"English","# Introduction\n## Metastasis background and requirements\n## Current models and limitations\n# Methods\n## zLiverMet model design and imaging\n## Cell lines and c-Met modulation\n## Applicability testing in colorectal cancer\n# Results\n## Efficient intrahepatic colonisation via IV injection\n## c-Met expression and liver tropism\n## Effects of c-Met overexpression and inhibition\n# Conclusions\n## Organism-on-a-chip implications and translational value","[{\"question\":\"What is the zLiverMet model and what does it measure?\",\"answer\":\"zLiverMet is a zebrafish larval intravenous-injection model built with a liver-specific fluorescent reporter to visualize and quantify tumour colonisation in the liver in vivo.\"},{\"question\":\"Why does the study focus on c-Met in liver tropism?\",\"answer\":\"The research tests whether c-Met activation drives the ability of cancer cells to preferentially colonise the liver, using cells with different c-Met expression/activation states and pharmacological inhibition.\"},{\"question\":\"How did SU11274 affect intrahepatic metastasis in the model?\",\"answer\":\"Inhibiting c-Met activation with SU11274 reduced intrahepatic liver colonisation induced by c-Met overexpression, indicating a functional role for c-Met signaling in liver tropism.\"}]","A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism | PDF",1790100104]