Relevant Factors Of Invasion And Metastasis Of Gastric Cancer

To observe Kiss-1, matrix metalloproteinase - 9 ( MMP-9 ) , FasL, Caspase-3, matrix metalloproteinase-7 ( MMP-7) expression and microvessel density ( MVD) in gastric cancer and explore their roles in progression of gastric cancer and their relevant molecular pathological mechanisms.MethodsKiss-1 mRNA expression was evaluated in gastric cancer and corresponding normal mucosa by RT-PCR. MMP-9 protein expression was examined by Western blot with its enzyme activity concerned. FasL, Caspase-3, MMP-7 expression and MVD were examined in gastric cancer or its corresponding normal mucosa by immunohistochemistry. These biological markers were compared with clinicopathological features of gastric cancer. The relationships between their expressions were analyzed as well.Results1. Kiss-1 mRNA expression level was lower in gastric cancer than that in normal gastric mucosa (P <0.05), whereas it was the converse for MMP-9 protein expression (P<0.05). Kiss-1 mRNA expression was negatively correlated with lymph node metastasis (P <0.05) ,whereas it was the converse for MMP-9 expression (P <0.05). Kiss-1 mRNA was less expressed in diffuse-type gastric cancers than that in intestinal-type ones (P <0.05). There was negative correlation trend between Kiss-1 mRNA expression and MMP-9 protein expression or enzymatic activity (P <0.05) , while positive correlation between MMP-9 pro-tein expression and its enzymatic activity (P <0.05).2. Primary cancer cells more frequently expressed FasL in gastric cancers than their adjacent epithelial cells ( P < 0. 05 ) , while it was the converse for Caspase-3 ( P < 0. 05 ). Infiltrating lymphocytes of primary foci showed strong immunoreactivity to Caspase-3 in 70. 8% of gastric cancers, more than their adjacent epithelial or cancer cells of primary foci (P <0. 05). FasL was less expressed in cancer cells of metastases than in those of corresponding primary foci ( P < 0. 05). It was the converse for Caspase-3 ( P < 0. 05). FasL expression was significantly correlated with tumor size, invasive depth, metastasis and differentiation in primary cancer cells (P <0. 05). FasL expression was higher in intestinal-type gastric cancers than that in diffuse-type ones (P <0. 05). FasL expression in primary gastric cancer cells paralleled positively with Caspase-3 expression in infiltrating lymphocytes of primary foci (P <0.05).3. MMP-7 showed positive expression in 29.2% of adjacent mucosa of gastric cancer, less than that in its gastric primary cancer (69.0% ). MMP-7 expression in primary foci was closely correlated with tumor size, invasive depth, metastasis and TNM staging of gastric cancer ( P < 0. 05). Positive correlation of mean MVD with tumor size, invasive depth, metastasis and TNM staging was found (P<0.05). Especially, mean MVD was dependent on MMP-7 expression in gastric cancer (P < 0. 05).Conclusions1. Down-regulated expression of Kiss-1 mRNA and up-regulated expression of MMP-9 protein were involved in gastric carcinogenesis. Altered expression of Kiss-1 mRNA and MMP-9 protein was closely correlated with lymph node metastasis of gatric cancer. Decreased expression of Kiss-1 mRNA was involved in invasion and metastasis of gastric cancer by enhancing protein expression and enzymatic activity of MMP-9.2. Up-regulated expression of FasL and down-regulated expression of Caspase-3 in primary cancer cells played an important role in gastric carcinogenesis. As an effective marker to reveal the pahobiological behaviors, FasL wasimplicated in differentiation, growth, invasion and metastasis of gastric cancer probably by inducing apoptosis of infiltrating lymphocytes. Protein derived from gastric primary cancer and metastatic microenvirongment might promote apoptosis of metastatic cells and eliminate immune counterattack by regulating Caspase-3 and FasL expression.3. Up-regulated MMP-7 expression played an important role in gastric car-cinogenesis. Altered expression of MMP-7 was an effective marker to reveal the pathobiological behaviors of gastric...