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Expression And Significance Of CXC Chemokine Receptor4 In Hepatocellular Carcinoma

Posted on:2008-06-13Degree:MasterType:Thesis
Country:ChinaCandidate:N LiFull Text:PDF
GTID:2144360218959025Subject:Hepatobiliary surgery
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BackgroundMetastasis is important character of malignant tumors and key point to difficultly cure malignant tumors that lead patient to death finally. In the most of Hepatocellular carcinoma patients, we observed that intrahepatic metastasis is one of the earliest characteristics of tumor metastasis. At present, it is still not cleared. Therefore, the research of molecular mechanism of malignant tumor is important to understood the development of tumor and search the effective method of treatment of tumor.Muller explained the relationship between chemokine receptors and breast cancer metastasis in 2001 and showed that expression of chemokine receptors were significantly associated with tumor metastasis. CXC chemokine receptor4(CXCR4)is one of most commonly chemokine receptors in tissue and plays important role in malignant tumors growth, migration and metastasis. CXCR4 is expresses higher in tumors than nomal tissues, and organs representing the main sites of tumor metastasis are the most abundant sources of its ligand stromal cell derived factor-1(SDF-1). Signalling through CXCR4 mediates actin polymerization and pseudopodia formation in cells, and induces chemotactic and migration to target organs. In addition, CXCR4-SDF-1 axis can promote tumor angiogenesis and growth. So chemokine receptor CXCR4 has become a new and attractive target for developing antitumor drugs.ObjectiveTo investigate the expression of CXCR4 in three hepatocellular carcinoma cell lines and its relationship with cell migration .MethodsBy semi-quantitative reverse transcription polymerase chain reaction, the expression of CXCR4 mRNA in three hepatocellular carcinoma cell lines(Huh7, HepG2,SMMC7721)were determined at the level of mRNA. By Western Blot, the expression of CXCR4 protein in three hepatocellular carcinoma cell lines were determined at the level of protein. By FACS, the expression of CXCR4 in three hepatocellular carcinoma cell lines were determined at the level of molecule. By cellular migration assays, relationship was analyzed between migration and the expression of CXCR4.ResultsInvestigation of CXCR4 is unification by RT-PCR, Western Blot and FACS, CXCR4 expression and transcription of human hepatocellular carcinoma cell lines varied from strong (SMMC7721,Huh7) to weak (HepG2). In vitro cellular migration assays, The chemokine SDF-1 can stimulated migration of SMMC7721 (P<0.01)and Huh7 (P<0.01) , but not of HepG2 (P>0.05).ConclusionExpression of CXCR4 in hepatocellular carcinoma cell is positive correlation with migration potentials. There was a significant increase migration in cell lines that express CXCR4 strongly with SDF-1.
Keywords/Search Tags:Receptor,CXCR4, SDF-1, Hepatocellular carcinoma, Migration, Metastasis
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