Studies on the antiinvasive character of TIMP-2 gene transfected gastric carcinoma cells*

AbstractAIM To investigate the change of ability in tumor invasion model of nude mice with matrixmetalloproteinase-2 (TIMP-2) gene transfected tissue inhibitor, and the expression pattern of tissue inhibitor of matrixmetalloproteinases/matrix metalloproteinases (TIMPs/MMPs).METHODS A full human TIMP-2 cDNA gene was constructed into virus rector PL-MT, and was transfered into human gastric carcinoma cells SGC7901 and positive clone was selected by G418. Tumor invasion model was established by Boyden chamber in vitro and subrenal capsule in vivo. The changes of TIMPs/MMPs were studied by immunohischemistry and in situ hybridization methods.RESULTS The expression of TIMP2 gene in SGC7901T2 cells was higher than the SGC7901 cells in vitro and the ability of invasion in Boyden chamber was weak in vitro. Type Ⅳ collagen was damaged in basement membrane of tumor invated lesions. The expression of membrane matrix metalloproteinase (MTMMP) in SGC7901T2 groups was higher than SGC7901 groups. The expression of TIMP-1, TIMP-2, MMP-2, MMP-9 and MT-MMP mRNA was not obviously changed in the two groups. The expression of MMP-2, MTMMP proteins in tumor tissues was closely related to the degree of tumor invasion.CONCLUSION The TIMP-2 gene may be an important negative factor in gastric carcinoma cell invasion and metastasis.