| Gastric cancer is one of the most common malignant tumors in China. Although it is treatmented by operation-based comprehensive therapies in recent years, the diagnosis is made at an advanced, and the five-year survival after resection of gastric cancer stays far below 50%. Invasion and metastasis are the main causes of death in patients with gastric cancer. Therefore, to study the mechanism of invasion and metastasis is most valuable in gastric cancer.The basement membrane (BM) and extracellular matrix (ECM) are the main barrier for tumor invasion and metastasis. The barrier is mainly composed of structural proteins and glycosaminoglycans. The former mainly includes collagen, laminin and fibronectin, whereas the latter chiefly consists of heparan sulfate proglycans (HSPGs). HSPGs is formed by a core protein and several covalent-binding heparan sulfate (HS) side chains, which has been attributed to a variety of biological effects that generally appear to be mediated through interactions the constituent polysaccharide chains and various molecules (e.g. growth factors, cytokines, lipoproteins and enzymes). In the past decade, the damage of structural proteins has been considered to be a critical step for tumor invasion and metastasis. The previous researches for gastric cancer mostly focused on property of some enzymes such as matrix metalloproteinases (MMPs), which use structural proteins as substrates. However, we should never neglect the effect of hydrolytic enzymes that use HSPGs as substrates, as well as their roles in degrading the BM and ECM. So far, heparanase is considered as a unique endoglycosidase degrading HSPGs. The cleavage of heparan sulfate chains is involved in the remodeling of ECM, and the release of heparansulfate-bound cytokines and growth factors, such as basic fibroblast growth factor and vascular endothelial growth factor, that may accelerate cancer cell invasion and metastasis directly or indirectly. So, the researches on the correlation between heparanase and invasion and metastasis in tumors are being carried out in recent years.It is well known that vascular endothelial growth factor (VEGF) is the most important inducer of angiogenesis and vessel permeability. Several additional members of the VEGF family have been identified, including VEGF-B, VEGF-C, VEGF-D, VEGF-E, and the placental growth factor (PIGF). VEGF-C is a ligand at the VEFG receptor (VEGFR)-3, also designated Flt-4. Flt-4 is a tyrosine kinase receptor which is expressed predominantly in the endothelium of lymphatic vessels. Alitalo and his colleagues reported that VEGF-C is a lymphoangiogenie factor that can selectively induce hyperplasia of the lymphatic vasculature.The roles of heparanase and VEGF-C in gastric cancer have not been clearly illustrated. In this study, we investigated the expression of heparanase and VEGF-C protein and their association with each other in gastric cancer.Materials and Methods1. Patients and tumor samplesParaffin-embedded archival samples from 97 patients with gastric cancer who underwent surgical resection at Zhejiang Province Hospital from Jan 1997 to Oct 2000 were by studied using immunohistochemisty (IHC). A control group includes 22 adjacent mucosas of gastric tumor and 20 normal gastric tissues. The clinicopathologic characteristics were evaluated according to the UICC standard published in 1997. Seventy-six patients were followed-up.2. ReagentsRabbit anti heparanase antiboby, rabbit and VEGF-C antibody3. Immunohistochemistry methodStreptavidin-peroxidase (S-P) two-step method was used for the immunohisto-chemical detection of Heparanase and VEGF-C proteins.4. StatisticsStatistical analyses were done with the SPSS 10.0 for Windows program. Correlation of heparanase or VEGF-C protein expression with various clinicopathological parameters were analysed by the Pearson Chi-square test orFisher exact test. The relationships between heparanase and VEGF-C in gastric tumor tissues were evaluated statistically using the Pearson correlat... |
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