| Malignant tumor develope from the persistent and unregulated growth of cells under the influence of physical and chemical factors. The relationship between tumor and immunity is complicated. Tumors have several features, such as characterized antigen expression and metabolized production that make their recognition and destruction by the immune system. Otherwise like pathogens, cancers may also acquire mechanisms of immune evasion due to the evolutionary selection of clones that can survive in an immunocompetent host.T cells play an essential role in inhibiting tumor growth and eradicating cancer cells. In tumor immunity, T cells are activated by tumor cells or mature dendritic cells that express the appropriate MHC-peptide and costimulation molecule, including adhesion molecules. The absence of these molecules contributs to the immune evasion of tumor, by inhibiting immune recognize. Many studies in experimental systems, as well as in human patients, have revealed that alteration in the adhesion molecules of tumor cells correlates with tumor progression and metastasis. Ovarian cancer is a malignant tumor with high mortality rate. Like other malignant tumors, there is absence of adhesion molecules in ovarian cancer, which contributes to immuneevasion of the tumor and metastasis.OPCML (OBCAM) molecules are the adhesion molecule on the surface of cells, which belong to the immunoglobulin superfamily CAMs with three Ig-domains, indicating a GPl-anchor as the functional mode of integration to the neural membrane. OPCML, mainly expressing in the neural cells of cerebral cortex and hippocampi, contribute to the growth of dendrites and adhesion between cells. The function of OPCML in neural cells suggests that it may participate in the development of malignant tumor as adhesion molecule.There were three mechanisms for the absence of genes expression in tumors, that is, mutation, abbarent expression and promoter methylation. Different tumors present different mechanisms, and promoter methylation is an only prominent one in some tumors.Considering function of OPCML, we propose that promoter hypermethylation also participates in OPCML expression modulation.We detected expression of OPCML mRNA in ovarian epithelial carcinoma and investigated the relationship between OPCML expression and hypermethylation of their promoters in order to provide some clues for tumor gene therapy.MethodsTwenty normal ovarian tissues and 89 ovarian epithelial tumors (72 malignant ones, 17 benigns) were collected for detection, in Department of Gynecologic Oncology, Women's Hospital, Zhejiang University, between 7.1997 and 7.2003. The median age were 46.5 years (range, 38-58years) in normal ovarian tissues, 39.0 years (range, 21-70years) in benign ovarian epithelial tumors, and 51.5 years (rang, 32-78years) in malignant serous ovarian carcinomas. Ofthose there were 3 of high-differentiated, 8 of middle-differentiated and 44 of low-differentiated,. According to the F1GO criteria, there were 2 in stage , 17 instage II , 50 in stageIII and 3 in stage IV.Three ovarian carcinoma cell lines, SKOV-3 and CaOV3 were bought from ATT. 3AO was boughtOPCML gene expression was detected by RT-PCR. A 327bp sequence was found after RT-PCR if there OPCML mRNA in cells.We detected promoter hypermethylation by methylation-sensitive restriction-enzyme PCR. There were 8 motif for methylation-sensitive restriction enzyme (MSRE) in the sequence, 4 of Hap , 2 of Ace , 1 of Aat and Cftl3 respectively. MspI/Hpall isoschizomers digested Both CCGG motif in sequence, but they recognise different state of cytosine residue-Mspl cleaves both methylated and unmethylated DNA, while Hpall cleaves just the unmethylated motif. The DNA was also methylated by SssI methyltransferase (New England) as positive comparison. No production was found if no methylation, while a 559bp sequence was found if methylation.Results19.4% of ovarian epithelial carcinoma expressed OPCML mRNA, while 85% of normal ovarian tissue and 76.5% of benign ovarian tumor. T... |
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