Expression Of UPAR Mediatiate Invasion And Metasitasis Of Human Hepatocellular Carcinoma

Objective1.To investigate the expression of urokinase-type plasminogen activator receptor (uPAR) in hepatocellular carcinoma (HCC) tissue, the adjacent noncancerous tissue and normal liver tissue, and the correlationship between uPAR and clinicopathologic factors of HCC.2.Investigate the expression of uPAR in HCC cell lines Hep-3B (with poor metastatic ability) and SMMC-7721 (with powerful metastatic ability), and the invasive ability in vitro of Hep-3B and SMMC-7721, to discover the correlationship between the expression of uPAR in HCC cell lines and their invasive ability in vitro.3.Investigate the invasive and metastatic ability in vitro and in vivo of uPAR positive (uPAR+) group and uPAR negatve (uPAR-) group separated from SMMC-7721, to evaluate the effect of the expression of uPAR on invasive and metastatic ability of HCC cell lines.Methods1.Immunohistochemic (IHC) study for uPAR was performed on 50 cases of HCC tissue and adjacent noncancerous tissue, 10 cases of normal liver tissue, investigate the correlationship between uPAR and clinicopathologic factors (such as the level of defferentiation of HCC, capsule invasion and portal vein tumor embolism and the size of tumor ).2.The expression of uPAR in HCC cell lines Hep-3B and SMMC-7721 was detected by flowcytometry (FCM), and their invasive ability in vitro was compared by Boyden charmber invasion experiement.3.uPAR+ group and uPAR- group were separated from SMMC-7721 with stronger metasitatic ability by FCM, and their ability of invasion and metasitasis in vitro and in vivo were compared by Boyden charmber test and carcinogenesis and metastasis in nude mice.Results1.we found that the expression of uPAR was stronger in HCC tissue than in the adjacent noncancerous liver tissues and normal liver tissues, uPAR had a strong relationship with capsule invasion and portal vein tumor embolism(P<0.01), and had an inverse ratio to the level of defferentiation of HCC, but not the size of tumor, the degree of cirrhosis, sex, liver function, AFP, HBsAg and so on.2. By flowcytometry, we found that SMMC-7721 which had stronger metastasis ability had higher uPAR expression level than Hep-3B with lower metastasis ability, and the level was 45.5% and 0.05% respectively. the Boyden charmber invasion exprement proved that SMMC-7721 had higher invasive ability in vitro than Hep-3B(P<0.01)3.We found that the uPAR+ group had stronger invasive and metastatic ability than the uPAR-group in vitro and in vivo(P<0.01).Conclusion1.The overexpression of uPAR in HCC suggest that uPAR is an important feature of HCC, the expression of uPAR is closely correlated with the malignant biologic behavior of HCC, uPAR can become an effective clinic prognostic index of HCC .2.The fact that SMMC-7721 with stronger metastasis ability had higher uPAR expression level than Hep-3B with lower metastasis ability suggest that the expression of uPAR is an important feature of HCC cell lines which had strong metastasis ability.3.The uPAR+ group separated from SMMC-7721 had stronger invasive and metastatic ability vitro and in vivo than the uPAR-group also from SMMC-7721, it suggest that uPAR facilited the invasive and metastatic ability of HCC cells, uPAR proved a new target of anti-recurrence and metastasis of HCC.