The Phenomena And Mechanism Of Vasculagenic Mimicry In A Rat Model Of Chemically Induced Hepatocellular Carcinoma

【Objective】This issue is to observe the relationships between the formation of vasulagenic mimicry and hepatocellular carcinoma differentiation grade,invasion and metastasis , in the male SD rat model with metastatic potential of DEN & NMOR induced hepatocellular carcinoma. Using varied methods to compare the differntial expression of MMP-2,TIMP-2 between liver tissue specimens include hepatitis,cirrhosis,hepatocellular carcinoma and with intrahepatic metastasis, this study is to explain that the imbalance of MMP-2/TIMP-2 is correlated with vasculagenic mimicry formation in HCC.【Methods】Set up the male SD rat model with metastatic potential of chemically induced hepatocellular carcinoma;Use varied methods include hematoxylin-eosin staining,immunohistochemistry,scanning electron microscope to detect the formation of vasculagenic mimicry ;Use RT-PCR experiment to detect the different expression of MMP-2 and TIMP-2 mRNA in liver tissue specimens; Use Westernblot and immunohistochemistry experiments to detect the different expression of MMP-2 and TIMP-2 protein in liver tissue specimens; Compare the proportion relationship of MMP-2/TIMP-2 in varied HCC tissue specimens with or without vasculagenic mimicry.【Results】This study successfully constructed the male SD rats model with intrahepatic metastasis of DEN & NMOR induced hepatocellular carcinoma; Using varied methods, we successfully detected the phenomena of vasculagenic mimicry in HCC; The phenomena of vasculagenic mimicry is related to the HCC differentiation grade; lower grade HCC has more VM(61.3% vs. 8.3%, X2=9.75,P<0.05); The phenomena of vasculagenic mimicry is related to the HCC invasion and intrahepatic metastasis; HCC with more invasion and metastasis has more VM(60.7% vs. 2.0%, X2=6.51,P<0.05); The level of MMP-2 and TIMP-2 mRNA is progressive rising in the liver tissue specimens with hepatitis,cirrhosis,hepatocellular carcinoma and HCC with intrahepatic metastasis; The level of MMP-2 and TIMP-2 protein is progressive rising in the different liver tissue specimens with hepatitis,cirrhosis,hepatocellular carcinoma and HCC with intrahepatic metastasis; The imbalance of MMP-2/TIMP-2 is more severe, comparing the HCC with VM to the HCC without VM.【Conclusions】The phenomena of vasculagenic mimicry is related to the differentiation grade,invasion and intrahepatic metastasis of HCC , in the male SD rat model of DEN & NMOR induced ;The imbalance of MMP-2/TIMP-2 is correlated with vasculagenic mimicry formation in HCC.