Hepatoselüler karsinoma hücrelerinde organ spesifik ekstravazasyonda C-met yolağinin rolünün incelenmesi

HCC is the fifth most common cancer worldwide and the third cause of cancer deaths. Due to difficulties in diagnosis, many patients are diagnosed at late stages. HCC is associated with high mortality rate due to high recurrence, metastasis risk after surgical resection. c-Met signaling pathway mediates embryogenesis and organ regeneration, its aberrant activation can promote invasion, motility, proliferation, angiogenesis and evading apoptosis in several cancers including HCC. Recent data suggest that activation of c-Met signaling might be an important factor in the regulation of tumor metastasis. However, role of c-Met signaling in the organ specific extravasation is not defined. Lab-on-a-chip is integrated 3D cell culturing to study for tumor-microenvironment interactions, drug screening, studying metastatic patterns of cancer cells to distant organs. In this study, a Lab-on-chip device was used to mimic the extravasation capacities of SNU-449, SNU-398, SNU-398-Met HCC cells to investigate role of c-Met on the organ specific extravasation. Homing cells were THLE-2, BEAS-2B and HS-27A to represent liver epithelial, lung epithelial and bone marrow/stroma cells respectively. HUVEC cells were used to mimic endothelial barrier. As a result, activation of c-Met signaling is significantly increased organ specific extravasation of HCC cells and c-Met inhibitor SU11274 decreased extravasation rate of HCC cells approximately 70% in total. Our data support that c-Met signaling could play role in organ specific extravasation especially in intrahepatic metastasis and bone metastasis and SU11274 could be used as anti-cancer drug to prevent metastasis especially to prevent HCC and can be used for therapeutic purposes.