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Study On The Expression Of Ezrin And Its Role In Tumor Adhesion, Invasion And Portal Vein Tumor Thrombosis Formation In Hepatocellular Carcinoma

Posted on:2005-08-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q M SunFull Text:PDF
GTID:1104360125467473Subject:Surgery
Abstract/Summary:PDF Full Text Request
ObjectivesTumor metastasis is a multi-step process in which several molecules are involved. Micro tumor thrombosis is formated with homotype and iostype adhesion increasing after tumor cells entered blood vessels. Compared with single tumor cell, micro tumor embolus is convenient for tumor cells survival, invasion, metastasis and portal vein tumor thrombosis formation. In the process of cell adhesion and invasion, siginal conduction mediated by adhesion molecules induce cytoskeleton reorganization. Adhesion molecules on the cell surface redistribute dramatically from even condition to aggregation. This process is blocked when cytoskeleton reorganization is inhibited. So it is necessary for further investigation the relationship between adhesive molecules redistribution and cytoskeleton reorganization.Ezrin, a crosslink protein of cytoskeleton and transmemberane molecule, may play a key role in the control of cell morphology. It is over-expressed in many tumors such as pancreatic carcinoma, endometrium carcinoma, and esophageal carcinoma. Several researches showed that ezrin was significantly overexpressd in tumors with highly metastatic potential, whereas inhibition of ezrin by stable expression of short hairpin RNA or antisense constructs directed at ezrin, or an established dominant negative ezrin mutant reduces the metastatic capability of tumor cell lines significantly.When cells adhesion , the actin based cytoskeleton reorganizes beneath the cytoplasma membrane to facillitate the adhesion molecules aggregation. When ezrin bind the side branches of F-actin, it can promote actin to assemble and F-actin enlongate. Cytochalasin D can inhibit actin polymerization and actin based cytoskeleton remoding.The purpose of our study is to investigate the expression of ezrin in three human hepatoma cell lines and human hepatocellular carcinoma (HCC), and the role of ezrin in tumor adhesion, motility, invasion and portal vein tumor thrombosis formation. MethodsThis study was carried out in 3 human hepatoma cell lines, 9 specimens of benign liver disease and 41 specimens of HCC. The expression of ezrin mRNA and protein was invastigated by RT-PCR, western-blot and immunohistochemistry. The multi-immunofluorescence method was also used to invastigate the distribution and colocalization of ICAM-1 and CD44 with ezrin. Ezrin expression was inhibited by transfecting antisense oligonucleotide into cells with liposomes and actin polymerization was inhibited by cytochalasin D.Results Expression of ezrin mRNA in hepatoma cell lines and human HCC The expression levels of ezrin mRNA differed between high and low invasive ability groups in hepatocellular carcinoma. All of three HCC cell lines expressed ezrin, and the express levels are related to the invasive potential. The expression levels of ezrin mRNA in bengin liver tumor, low invasive group, high invasive cases, tumor thrombosis and liver tissue surrounding tumor were 0.6012±0.1672, 0.7116±0.1486, 0.9764±0.2148, 1.1225±0.3543 and 0.6841±0.2061 respectively. It suggested that ezrin was overexpressed in hepatocellular carcinoma (P<0.05), and ezrin expression in high invasive HCC group was higher than that in low invasive group, portal vein tumor thrombosis expressed the more ezrin than their primary tumor and high invasive group (P<0.05).Expression of ezrin protein in hepatoma cell lines and human HCC Three HCC cell lines all expressed ezrin, and the expression levels were correlated with the invasive potential. 3 of 9 cases benign tumor are positive stained(33.3%), Ezrin was detected in 26 of 29 (89.7%) cases of high invasive group, while only 7 of 12 in low group are positive(58.3%). 15 of 16 high invasive cases with PVTT were positive(15/16, 93.8%), 11 of 13 high invasive cases without PVTT were positive(11/13, 84.6%). and 14 cases of tumor thrombosis are positive (14/16,87.5%). These indicated that ezrin was overexpressed in hepatocellular carcinoma compared with adjacent liver tissue (P<0.05), and the high invasive gr...
Keywords/Search Tags:Ezrin, Hepatocellular carcinoma, Portal vein tumor thrombosis, Actin based cytoskeleton, Adhesion, Invasion
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