Expression Of E-cadherin, MMP-2, TIMP-2, C-Src In Gastric Carcinoma: Exploration Mechanism Of Invasion And Metastasis

Objective: The purpose of this study was to investigate the expression of E-cadherin,MMP-2,TIMP-2,c-Src in gastric carcinoma.In order to explore the role of E-cadherin,MMP-2,TIMP-2,c-Src in the metastasis and invasion of gastric carcinoma.Methods: 50 gastric carcinoma samples were analyzed and meanwhile 10 normal gastric mucosa samples were study as controls . All subjects were the admitted pations for operative treatment. S-P method were used to detect the expression of E-cadherin,MMP-2 of all samples ;and Flow cytometry (FCM)were used to detect the expression of TIMP-2,c-Src of all samples .Results: 1. E-cadherin expression in gastric carcinoma (46%) were significantly lower than in normal gastric mucosa (100%) (p<0.001). The positive rate of E-cadherin in non-metastatic group(35.29%) was higher than that in metastatic group(68.75%)(p<0.05).The expression of E-cadherin in stages Ⅰ-Ⅱ and T1-T2 were significantly higher than those in Ⅲ-Ⅳ and T3-T4 (respectively p<0.05). And also the significant correlationship was observed between E-cadherin expression and histological grade(p<0.05). The positive rate of E-cadherin in poorly differentiated group was significantly lower than that in well differentiated group.No relationship was observed among E-cadherin expression and sex, age, further metastasis.(p>0.05) 2 The positive rate of MMP-2 protein in gastric carcinoma was 74%,whereas hardly found in normal gastric mucosa.There was significant difference between them(p<0.05).The high expression of MMP-2 was related to tumor metastasis.There was a significant correlation between high MMP-2 expression and degree of differentiatiation ( p<0.05).The positive rates of MMP-2 in stages Ⅰ-Ⅱ were significantly lower than that in stages Ⅲ-Ⅳ(p<0.05).MMP-2 expression was higher in T3-T4 than that in T1-T2 (p<0.001). 3. The expression of c-Src in gastric carcinoma was significantly higher than that in normal gastric mucosa( p<0.01).The FI (Fluorescence index) value of c-Src protein in metastatic group was 1.346±0.299, the positive expression rate was 91.18%, whereas in non-metastatic group respectively was 1.140±0.193,62.5%. There was significant difference between them(p<0.05) The expression of c-Src in stagesⅠ-Ⅱ and T1-T2 were significantly lower than those in Ⅲ-Ⅳ and T3-T4 (all p<0.05).Significant correlationship was observed between c-Src expression and histological grade. The positive rate of E-cadherin in poorly differentiated was significantly higher than that in well differentiated. 4.TIMP-2 protein expression in gastric carcinoma was significantly higher than that in normal gastric mucosa(p<0.01),whereas no relationship was observed between TIMP-2 and tumor metastatic in gastric carcinoma.The expression of TIMP-2 protein correlated only with TNM classification.No relationship were found among TIMP-2 and other pathological characteristics. 5.The expression of E-cadherin was high reversely correlated with MMP-2(r＝–0.368,p<0.009). There was reversely correlated tendency between MMP-2 and TIMP-2 in clinical stage, depth of invasion , further metastasis, but no significant association was found(p>0.05).There were no significant association among other ptoteins expression. Conclusion: The over-expression of MMP-2,TIMP-2,c-Src were examined in gastric carcinoma, E-cadherin on the opposite.The lower expression of E-cadherin possibly related to metastasis and invasion of carcinoma,E-cadherin may also prove to be a useful marker for determing the biological aggressiveness of gastric carcinoma. c-Src was coimmunoprecipitated with E-cadherin–catenin complex, cell-cell adhesion was inhibits possibly through c-Src activation The over-expression of c-Src was correlated with invasion and metastasis of gastric carcinoma.The over-expression of MMP-2 and TIMP-2 may play a key role in invasion and metastasis of gastric carcinoma.