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OPN Signal Transduction Is Involved In Invasion And Matastasis Of Colorectal Carcinoma

Posted on:2006-12-20Degree:MasterType:Thesis
Country:ChinaCandidate:X L SongFull Text:PDF
GTID:2144360152481841Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:The colorectal carcinoma is one of familiar malignancies in china. Its incidence is rising year by year with the improvement of people's living condition, the change of dietary patttern, the quickness of life pace. There might be some effects by operation, chemotherapy, radiotherapy and other general therapy, but data shows that about 30 percent patients die of repea and distant metastasis. Recently, with the development of tumor molecular biology, intercellular signal transduction has become popularly concentrated on biological proplem. Not only it regulates cellular growth, development, multiplocation, death and so on, but also is colsely related to maligancies, such as colorectal carcinoma. The adhesion of tumor cell to extracellular matrix(ECM) is a dynamic and adjustive state, which supply with tumor cell from each other. Tumor's invasion begin with single tumor cell shedding from primary tumor. The essence is the loss of adhesive molecules, thus tumor cell acquires metastasis potent. As the ligand of tumor cell's adhesive molecule, large molecullar protein of ECM combines with tumor cell firstly, litterly basement membrane degrades, and tumor cells tranfer. Osteopontin(OPN) attributes to one of proteins of ECM. Recent studies show that OPN is involved in liver metasasis of colorectal carcinoma. The functional domain of OPN is Arg-Gly-Aap(RGD) sepuence. This pathologicl process is accomplished by OPN interacting with its receptor, that is integrin. As the receptor of ECM protein, integrin not only mediates interaction between cell and ECM, cell and cell, but also integrates extracellular irritating signals into cell. Focal adhesion kinase(FAK) is a mediator of linking integrin with subordinate signals, a joint of many signal pathways. Phosphatidylibositol-3 kinase(PI-3K) is one of extending parts of β3-FAK signal transduction pathway. PI-3K plays a important role in the process of cell growth, differentiation and metastasis, sending activated signals into cell by phosphating PI. At present, there are no reports about the expression of OPN, β3, FAK, PI-3K in colorectal carcinoma, the relationship among them, and their functions in the metastasis process of colorectal carcinoma. Immunohistochemistry staining is used to observe and analysis expressive characteristic of OPN, β3, FAK, PI-3K and the relationship between them in colorectal carcinoma tissues, investigating their pertinence to coloretal carcinoma, in order to afford valuable references for clinical treatment and prognosis. Methods: 1 Specimens: 30 cases of colorectal carcinoma specimens and paired normal tissues were collected from patients operated in the Surgery Department of the Fourth Hospital of Hebei Medical University during March 2003 to september 2003. Allspecimens were verified by pathology. The distance from carcinoma to normal tissue was at least 10 centimeters. All specimens were collected within half an hour after the operation and made into paraffin sections. 2 Immunohistochemistry staining was used to detect the expression and distribution of OPN, integrin β3, FAK and PI-3K in normal and colorectal carcinoma tissues. The experiment procedures were according to the Test Kit introduction. The paraffin sections were incubated with polyclonal antibody of anti-OPN(1:16 dilution), monoclonal antibody of anti-β3(1:400 dilution), monoclonal antibody of anti-FAK(1:50 dilution) and polyclonal antibody of anti-PI-3K(1:200 dilution). Results: 1 The positive particles of OPN were mainly distributed at the stroma cells of nomal tissues. There was also a little distribution at the gland cells. It showed that normal tissues can expressed OPN, which mainly distributed in stroma cells. However, tumor tissues were very different from normal tissues. The positive particles of OPN were mainly distributed at the cytoplasm of tumor tissues, in which the quantity of them at the stroma cells was significantly less than that at the cytoplasm cells. There were no or a little OPN in stroma cells of tumor tissues. The results seggested that the ability of maligant tumor cells expressing OPN increases and that OPN played an important role for maintaining tumor's growth. 2 The positive particles of integrin β3 were mainlydistributed at the cytoplasm cells of nomal tissues. The expression level of it was medium in normal tissues, and decreased significantly in tumor tissues. The deta showed that integrin β3 is not main receptor mediated adhesion in coloretal carcinoma. In the process of tumor cell's adhering and metastasis, there might be other types of integrin receptor. 3 FAK and PI-3K were the intercelluar extending parts of integrin-mediating-transmembrane signal transduction. The expression level of them was significantly higher than that in normal tissues. Conclusions: The appearness of brown particles under the microscope is regarded as positive staining. Results show that the positive particles of OPN are mainly distributed at the stroma cells of normal tissues. There is also a little distribution at the gland cells. However, they are mainly distributed at the cytoplasm of tumor tissues, in which the quantity of them at the stroma cells is significantly less than that at the cytoplasm cells. OPN has positive relationship with coloretal carcinoma. The expression level of integrin β3 in normal tissues is medium, which decreases obviously in tumor tissues. There is no evidently relationship between integrin β3 and coloretal carcinoma.The positive particles of FAK in colorectal carcinoma tissues are much more than those of normal tissues. PI-3K can hardly be detected in normal tissue, but in tumor tissues, its expression level increases significantly. With the progression of tumor, the...
Keywords/Search Tags:coloretal carcinoma, osteopontin, integrin β3, focal adhesion kinase, Phosphatidylibositol-3 kinase
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