Clinical Significance Of Syndecan-1 And MMP-1 Expresssion In Gastric Cancer

Introduction:Gastric carcinoma is one of the most frequent occurred malignant tumors in China. Although it is cured by operation-based comprehensive therapies, the five-year survival rate following curative resection is still about 40 percent in recent years. Because most gastric cancers are categorized as developing stage when they are diagnosed in clinic, the figure remains high. Cancer invasion and metastasis are the main causes of patient death. Therefore, studying its invasion and metastasis are most valuable as well as diagnosis and treatment in early stage.The process of cancer invasion and metastasis comprises a complex series of sequential steps involving tumor cell-host cell and cell-matrix interactions. It is revealed that syndecans and MMPs play important roles during the process of invasion and metastasis. Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans(HSPGs), which synthesized by many cells. It is found mainly in epithelial cells. Syndecan-1 is type I transmembrane proteins, with an N-terminal signal peptide, an ectodomain, a single hydrophobic transmembrane domain and a short C-terminal cytoplasmic domain. Syndecan-1 has several important consequences, as indicated below. First, it is essential regulator of ligand-dependent activation of primary signallingreceptors at the cell surface. Syndecan-1 accomplishes this by binding, via their covalently attached glycosaminoglycan chains, extracellular ligands for primary signalling receptors at the cell surface. Second, syndcan-l has been suggested to play a role in cell-cell adhesion, base on the finding that several well-characterized cell-adhesion molecules bind heparan sulphate. It has been shown that certain human myeloma cell lines have lost their ability to synthesize syndecan-1. The loss of syndecan-lexpression correlates with the inability of the cells to adhere to one another in a rotation-mediated aggregation assay. Stable transfection of these cells with syndecan-1 cDNA restores cell-cell adhesion activity. Third, Syndecan-1 is related with cell migration. Cell migration is a complex activity that is dependent on interaction of cells with an adhesive surface and mediated by directed membrane and cytoskeleton assembly. Studies with cultured cells have shown a close correlation between cell-substratum adhesive strength and migration rates. Evidence for a role of syndecan-1 in modulating cell-migration activity comes from studies of lymphocyte migration. As described above, some lymphocyte cell lines lose syndecan-1 expression. These cells exhibit markedly enhanced rates of migration through collagen gels. Transfection of these cells to restore syndecan-1 expression produces a significant reduction in migration rates. Fourth, syndecan-lexpression appears to be required for maintenance of a differentiated epithelial phenotype and suppression of tumor growth.The matrix metalloproteinases (MMPs) are a family of twelve secreted and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix, including fibrallar and non-fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins. Interstitial collagenase (MMP-1) can degrade collagen type I> II> III. Immunostaining showed localization of MMP-1 protein in the stromal cells, and additionally in the neoplastic glands. These findings indicate that the stromal cells may play an importantrole in the expression of MMP-l, and suggest a pathophysiological role for MMP-1 in the invasion and metastasis of gastric cancer. Murray GI indicate that MMP-1 detected in 73% of gastric cancer. Tnoue T found that MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a...