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The Expression Of Cathepsin B,Laminin And Syndecan-1 In Esophageal Squamous Carcinoma And Its Relationship With The Invasion,Metastasis

Posted on:2008-06-16Degree:MasterType:Thesis
Country:ChinaCandidate:X Q CaoFull Text:PDF
GTID:2144360215460140Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Cathepsin B is a lysosome cysteine proteinas of papain family. CB distributes in human liver, spleen, kidney, bone, nerve cell, matrix fibroblast, macrophage and so on, In the condition of neutral and acidity, CB is active and inactive irreversibly in the alkaline environment. The role of CB is extremely extensive, CB participates in many sorts of physiologic function such as osmogen activation, antigen processing and tissue remodeling, especially bone matrix absorption and so on and pathological process. It is especially important that CB could degrade directly or activate plasminogen activator and matrix metalloproteinase et al degrade indirectly many extracellular matrix and basement membrane components for example Laminin, fibronectin and type IV collagen and so on, destroying the integrity of its structure thus promoting the infiltration and metastasis of tumor. Recently mass researchs indicate CB shows high expressions in many kinds of malignant tumors such as lung cancer,breast cancer, carcinoma of prostate, gastric cancer, liver cancer, adenocarcinoma of esophagus, melanoma, neurogliocytoma and so on, moreover its expression and activity are higher twice even 3-9 times than adjacent normal tissues,Besides, CB participates in occurrence, development and new Angiogenesis, furthermore transcription, evels of expression are posive correlation with the prognosis of tumor. Laminin, which is mainly synthesized and secreted by endothelial cells and endothelial cells is a kind of non-collagen glycosidoprotein of extracellular matrix and basement membrane components. It reacts with cells by high affinity Laminin receptor, thus mediatingadhesions between cells with basal membrane. There is study, which indicates, LN plays the important roles in cell proliferation, differentiation, migration, embryonic development, nerve growth, occurrence, infiltration, metatasis of tumor and maintaining structure integrity of basal membrane and so on. In the recent years people discover that the roles of adhesion molecule in infiltration and metastasis of tumor are non-neglectful, therefore paid close attention to. Syndecan-1 is fundermental adhesion molecule and plays the important roles during this process. Syndecan-1 is a kind of heparan sulfate proteoglycan and belongs to a member of adhesion molecule integrin glutinous proteoglycans family, residing in endothelial cell surface of majority and mediating the ligation between celluar surface and extracelluar ligand, thus leading to stability of cell adhesion and concerned with the migration of cell and maintain differentiated phenotype and suppress the growth of tumor, The research discovered that Syndecan-1 express low or get loss in human many varieties of malignant tumors, thus promotint growth, infiltration and metastasis.Esophageal carcinoma is frequent one of the malignant tumors, Henan province has high incidence rate, invasion and metastasis is main death reasons of esophageal carcinoma patients, Therefor exploring the mechanism of the invasion and metastasis of esophageal carcinoma has been one of research hot spots. How CB and LN,Syndecan-1 and its relationship with the invasion and metastasis of esophageal carcinoma as well as mutual relationships among them researchs, to this date domestic and foreign documents havenot reports. In order to discuss the mechanisms of esophageal carcinoma , seach valid methods, which can suppress the infiltration and metastasis of esophageal carcinoma and extend survival time of esophageal carcinoma patients. Our research adopts immunohistochemistry and in situ hybridization method, observing the expressions of CB and Syndecan-1 protein and mRNA in esophageal carcinoma tissues of 49 cases,adjacent non-atypical hyperplasia tissues of 30 cases and normal mucosa tissues of 49 cases; adopting immunohistochemical methods to investigate the expression of LN protein. Our research explores furtherly the mechanisms of infiltration and metastasis of esophageal carcinoma and provides theory foundation for blocking invasion and metastasis of esophageal carcinoma. Methods1. Using the technology of immunohistochemistry SP to detect the expression of CB and Syndecan-1, LN in the 49 cases of esophageal squamous cell carcinoma, 30 cases of atypical hyperplasia tissues of tumor-adjacent and 49 cases of normal mucosa of esophageal carcinoma respectively.2. Using the technology of in situ hybridization to indicate the gene of CB and Syncecan-1 in 49 cases of esophageal squamous cell carcinoma, 30 cases of atypical hyperplasia tissues of tumor-adjacent and 49cases of normal esophageal tissues respectively.3. Statistical analysis: All the dates were analyzed by SPSS 11.0 statistical package, the count information calculated the positive rate, The comparison of positive rates uses the Chi-square;The relation of two variable were analyzed by the spearman level correlation analysis.The level of significant difference wasα=0.05.Results1. In the metastatic and non-metastatic group, the positive rates of expressions of CB protein and mRNA were 20(100.00%), 18(62.07%) and 19(95.00%), 16(55.20%) respectively, there was a significant difference between the two groups with the expressions of protein or mRNA of them (P both<0.05); The positive rates of expressions of CB protein and mRNA on the low-muscle invaded, deep-muscle invaded and outer lay invaded were 5(50.00%), 9(60.00%), 24(100.00%) and 4(40.00%), 8(53.33%), 23(95.83%) respectively, the expressions of their protein and mRNA in the carcinoma tissues with the outer lay invaded were higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was a significant difference among the groups(P all<0.05); The positive expressions of CB protein and mRNA in the tissues of esophageal carcinoma, atypical hyperplasia of tumor-adjacent and nomal tissues were 38(77.55%), 8(26.67%), 0(0.00%) and 35(71.43%), 7(30.43%), 0(0.00%) repectively; the positive rates of expressions of their protein or mRNA in the carcinoma tissues were compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, There was statistital significance( P all <0.05).2. The positive rates of expressions of Syndecan-1 protein and mRNA were 5(25.00%), 18(62.07%) and 4(20.00%), 17(58.62%) respectively, there was a significant difference between the two groups with the expressions of protein or mRNA of them (P both<0.05); The positive rates of expressions of CB protein and mRNA on the low-muscle invaded, deep-muscle invaded and outer lay invaded were 8(80.00%), 9(60.00%), 6(25.00%) and 7(70.00%), 9(60.00%), 5(20.83%) respectively, the expressions of their protein and mRNA in the carcinoma tissues with the outer lay invaded were lower than that in the tissue with low-muscle invaded and deep-muscle invaded. There was a significant difference among the groups(P all<0.05); The positive expressions of Syndecan-1 protein and mRNA in the tissues of esophageal carcinoma, atypical hyperplasia of tumor-adjacent and nomal tissues were 23(46.94%), 23(76.67%), 49(100.00%)和21(42.86%), 20(66.67%), 49(100.00%) respectively, the positive rates of expressions of their protein or mRNA in the carcinoma tissues were compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, There was statistital significance( P all <0.05).3. The positive rates of expressions of LN protein were 3(15.00%) and 23(79.31%), There was a significant difference between the two groups with the expressions of protein or mRNA of them (P both<0.05); The positive rates of expressions of CB protein on the low-muscle invaded, deep-muscle invaded and outer lay invaded were 9(90.00%), 12(80.00%), 5(20.83%) respectively, The expressions of their protein and mRNA in the carcinoma tissues with the outer lay invaded were lower than that in the tissue with low-muscle invaded and deep-muscle invaded. There was a significant difference among the groups(P all<0.05); the positive expressions of LN protein in the tissues of esophageal carcinoma, atypical hyperplasia of tumor-adjacent and nomal tissues were 26(53.06%), 23(76.67%), 49(100.00%),the positive rates of expressions of their protein in the carcinoma tissues were compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, There was statistital significance( P all <0.05).4. The relativity of the expression of CB and Syndecan-1 LN was analysized by statistics, Results showed that the former is also negative correlation with later both(r both<0,P<0.05), There is a positive correlation between later both(r>0,P<0.05).Conclusions1. The expressions of CB protein and mRNA in human esophageal squamous cell carcinoma showed an obivious increasing, There were comparisons of the expressions of CB protein or mRNA among different tissues, different depth of invasion and metastasis and non-metastasis , the difference had significanc. The high expressions of CB might be relative to development, invasion and metastasis of esophagealcarcinoma.2. The expressios of Syndecan-1 protein and mRNA in human esophageal squamous cell carcinoma showed increasing or missing, There were comparisons of the expressions of Syndecan-1 protein or mRNA among different tissues, different depth of invasion and metastasis and non-metastasis, the difference had significanc. It indicated that low expressions of Syndecan-1 might facilitate development, invasion and metastasis of esophageal carcinoma.3. The expressions of LN protein in human esophageal squamous cell carcinoma expressed lower increasingly, There were comparisons of the expressions of LN protein or mRNA among different tissues, different depth of invasion and metastasis and non-metastasis, the difference had significanc. The low expressions of LN might play the important roles in the development, invasion and metastasis of squamous carcinoma of the esophagus .4.The relativity of the expression of CB,Syndecan-1 and LN protein was analysized by statistics, Results showed relative and they might play synergistic effects during the process of occurrence and development and infiltration, metastasisof squamous carcinoma of esophagus.
Keywords/Search Tags:Squamous carcinoma of esophagus, Non-hyperplasia, CB, Syndecan-1, LN, Infiltration, Metastasis
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