SPOCK1 EXPRESSION IN LIVER REGENERATION, CIRRHOSIS AND HEPATOCELLULAR CARCINOMA
Váncza Lóránd
Pathological and Oncological Divison
Dr. Matolcsy András
SE I.sz. Patológiai és Kísérleti Rákkutató Intézet tanterme
2026-06-23 14:00:00
Molekuláris és experimentális onkológia
Dr. Bödör Csaba
Dr.Kovalszky Ilona,Dr. Dezső Katalin
Dr. Halász Judit
Dr. Forika Gertrud
Dr. Mandl József
Dr. Jakab Anna
Dr. Ferencz Bence
SPOCK1 is a CSHS-PG that is overexpressed in several types of cancer and this correlates with poor prognosis. Under normal conditions it is highly expressed in certain regions of the brain, it has been also detected in the heart, skeletal muscle, prostate and testis, but not in the normal liver. It is also involved in the development of the blood-brain barrier and in the adipocyte differentiation and maturation. Its known transcription factor is CHD1L and it interact with the integrin α5β1 receptor. It is involved in the EMT, remodeling of the ECM trough activation of MMP2 and MMP9, and activates the AKT and Wnt/β-catenin signaling pathways.
Our objective was to investigate the role of SPOCK1 in physiological and pathological conditions of the liver.
We found that SPOCK1 is expressed in the hepatocytes adjacent to the portal and central veins in normal human liver and exhibits a cytoplasmic granular staining pattern. It co-localizes with mitochondrial markers on immunofluorescent staining. It is highly expressed in isolated primary rat hepatocytes but not in the Lx2 human hepatic stellate cell line in co-culture. High SPOCK1 expression was observed in dedifferentiated proliferating hepatocytes in human liver regeneration after massive hepatic necrosis. Its level was significantly increased in HCV-related cirrhosis and HCC and in silico analysis revealed that increased SPOCK1 expression in HCC correlated with shorter overall survival. Increased SPOCK1 and CHD1L expression was observed in the foci in DEN induced mouse model of hepatocarcinogenesis. We found that SPOCK1 is secreted into the culture medium of the HCC cell lines, and increased levels of SPOCK1 were also found in the serum of patients with HCC. Overexpression of SPOCK1 in HepG2 cell line increased the BrdU labeling index, whereas silencing of SPOCK1 in HLE and Huh7 cell lines decreased the BrdU labeling index. Phosphokinase array revealed that silencing SPOCK1 significantly decrease the level of EGFR, ERK1/2, TOR(S2448) and Yes in HLE and Huh7 cell lines.
SPOCK1 is present in the normal liver and its level is increased in liver regeneration also significantly increases in liver cirrhosis and HCC. Together with our in vitro data this suggest that SPOCK1 might contribute to the development and progression of HCC.
