| The liver metastasis of human colorectal carcinoma (HCC) is the main reason that this kind of patient with HCC died. Efficiently blockade the way that tumor metastasis is the key that could ascend the viability, prolong the viability, and effect a radical cures this disease, beside the method of surgical. The abilities of the growth and invasion that uncontrolled, were dependent on that cancer cell could be progress absoluteness itself, invasion and destroy irretrievability the tissues around it, and insobriety snatch nutrient from the tissues beside. Tumor-cell metastasis is the result of several phase and multistep cascade, among other parameters, processes such as the proliferation, adhesive, invasion, and angiogenesis. At the end of 70s, it is found that the metastasis of tumor was relativity with a sore of substance like heparin. Although these phenomena well-documented, it has takes 20 years to isolate a heparanase gene, mainly because of instability in designing specific, quantitative assays. Cloning and functional characterization of the long sought-after heparanase opens a new chapter in the understanding andpotential manipulation of metastasis processes. Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPG), localized in the extracellular matrix and on the external surface of cell membranes, play a major role in cell-cell and cell-extracellular matrix interactions. It is the important constituent parts of basement membranes. HSPG are implicated in a number of cellular processes, including cell adhesion, migration, differtiation, and proliferation. Heparanse is an endo- P -D-glucuronindase that degrades the HS side chains of HSPGs in MEC, cleaves the network structure of basement membranes(BMs) , and been implicated in inflammation and tumor angiogenesis and metastasis. In this study, we used the method of ISH, immunohistochemistry, gene transfection, cell culture, metastasic animals model, in order to clarity the mechanism of hepaeanase and basement membrane proteins in tumor metastasis and screen new drug candidates for cancer therapy, heparanase anti-sense oligodexynucleotide (ASODN ) and laminarin, an inhibitor that can integrate with heparanase were experimented to inhibit the ability of invasion and metastasis.Mainly studies included:1. To explore the expression of heparanase mRNA by ISH and the laminin and laminin receptor by immunohistochemistry in the human colorectal carcinoma tissues and metastasis lymph node, carcinoma metastasis liver and villiform adenoma, investigated the role and correlations of them in the metastasis of colorectal carcinoma; and investigate the role and correlations of them in the metastasis of colorectal carcinoma.2. With the method of gene transfection to transform the full-length human heparanase cDNA to human colorectal cell lines HT29 with lepofection 2000, that is the lower metastasis capability cell line. To prove heparanase has an important role in generation and metastasis.3. Liver metastasic model simulating human colon cancer was established by orthotopic implantation of histologically intact human tissue intocolon wall of node mice. Incidence of liver metastasis were observed. The different of tumor sizes, modality, structure, and angiogenesis between two groups were analyzed.4. The expression of heparanase mRNA among the different colorectal cell lines, that were lower or higher ability of metastasis were detected.5. Laniinarin, an inhibitor that can integrate with heparanase was experimented to inhibit the ability and content of heparanase. It reduces cleaving of heparan sulfate, protects ECM, and prevents invasion and metastasis of tumor.6. Heparanase anti-sense oligodexynucleotide (ASODN ) that was transfected to the HCC cell, inhibit the cell proliferation in vitro. The aim of this study was investigation the effect hi vitro of antisenes oligodeoxynucleotided of heparanase on its gene expression and cell proliferation and invasion capacity of HCC HT29 cells lines.Th...
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