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

Bagci G., Comez D., Topel H., Yilmaz Y., Bagirsakci E., Gunes A., ...More

Biochimica et Biophysica Acta - Molecular Cell Research, vol.1870, no.8, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Letter
  • Volume: 1870 Issue: 8
  • Publication Date: 2023
  • Doi Number: 10.1016/j.bbamcr.2023.119557
  • Journal Name: Biochimica et Biophysica Acta - Molecular Cell Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: c-Met, Extravasation, HCC, Lab-on-a-chip (LOC), Metastasis, Microenvironment
  • Dokuz Eylül University Affiliated: No


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.