c-Met activation promotes extravasation of hepatocellular carcinoma cells into 3D-cultured hepatocyte cells in lab-on-a-chip device

Gulsun Bagci; Dehan Comez; Hande Topel; Yeliz Yilmaz; Ezgi Bagirsakci; Aysim Gunes; Gizem Batı Ayaz; Ismail Tahmaz; Muge Bilgen; Gulhas Solmaz; Devrim Pesen Okvur; Nese Atabey

doi:10.1016/j.bbamcr.2023.119557

c-Met activation promotes extravasation of hepatocellular carcinoma cells into 3D-cultured hepatocyte cells in lab-on-a-chip device

Biochim Biophys Acta Mol Cell Res. 2023 Dec;1870(8):119557. doi: 10.1016/j.bbamcr.2023.119557. Epub 2023 Aug 5.

Authors

Affiliations

¹ Izmir Biomedicine and Genome Center (IBG), Balcova, 35340 Izmir, Turkey; Department of Molecular Biology and Genetics, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Balcova, 35340 Izmir, Turkey.
² Izmir Biomedicine and Genome Center (IBG), Balcova, 35340 Izmir, Turkey; Department of Medical Biology and Genetics, Graduate School of Health Sciences, Dokuz Eylul University, Balcova, 35340 Izmir, Turkey.
³ Izmir Biomedicine and Genome Center (IBG), Balcova, 35340 Izmir, Turkey.
⁴ Biotechnology and Bioengineering Graduate Program, Izmir Institute of Technology, Gulbahce, Urla, 35430 Izmir, Turkey.
⁵ Izmir Tinaztepe University, Galen Research Center, Buca, 35400, Izmir, Turkey.
⁶ Department of Molecular Biology and Genetics, Izmir Institute of Technology, Gulbahce, Urla, 35430 Izmir, Turkey.
⁷ Izmir Biomedicine and Genome Center (IBG), Balcova, 35340 Izmir, Turkey; Izmir Tinaztepe University, Galen Research Center, Buca, 35400, Izmir, Turkey; Izmir Tinaztepe University, Faculty of Medicine, Department of Medical Biology and Genetics, Buca, 35400 Izmir, Turkey. Electronic address: nese.atabey@ibg.edu.tr.

PMID: 37549739
DOI: 10.1016/j.bbamcr.2023.119557

Abstract

Activation of c-Met signaling is associated with an aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC); however, its contribution to organ preference in metastasis remains unclear. In this study, using a Lab on a Chip device, we defined the role of aberrant c-Met activation in regulating the extravasation and homing capacity of HCC cells. Our studies showed that (i) c-Met overexpression and activation direct HCC cells preferentially towards the hepatocytes-enriched microenvironment, and (ii) blockage of c-Met phosphorylation by a small molecule inhibitor attenuated extravasation and homing capacity of HCC cells. These results, thus, demonstrate the role of c-Met signaling in regulating the colonization of HCC cells preferentially in the liver.

Keywords: Extravasation; HCC; Lab-on-a-chip (LOC); Metastasis; Microenvironment; c-Met.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / pathology
Cell Line
Hepatocytes
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / pathology
Tumor Microenvironment