Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase 1 gene in nude mice

Cancer
M WatanabeM Seiki

Abstract

Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of matrix metalloproteinases (MMPs) that degrade extracellular matrix. We evaluated the metastatic ability of the highly metastatic human gastric cell line KKLS, and that of cells transfected with exogenous TIMP-1 gene by the orthotopic transplantation model in nude mice. KKLS was derived from human gastric cancer. Expression of mRNA for tissue inhibitor of metalloproteinase-1 (TIMP-1) was almost undetectable in KKLS cells. KKLS cells were transfected with exogenous TIMP-1 gene by the Chen-Okay-ama method. Two clones (KTCLs) that expressed different levels of TIMP-1 and neomycin-resistant KKLS (K-neo) were obtained. The KKLS cells and these transfectants were orthotopically transplanted into nude mice (murine stomach) and metastasis in the murine liver was detected. As a method of detecting metastasis, we used a DNA fragment (human beta-globin gene) specific to human tumor cells that have metastasized into the murine liver by polymerase chain reaction (PCR). Differences in tumor growth in the murine stomach were not observed between KKLS cells, K-neo cells, and the two transfectants expressing the different TIMP-1 levels (low, KTCL-1; high, KTCL-14). The...Continue Reading

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Citations

Nov 21, 1998·Gut·G I MurrayJ E Fothergill
May 20, 2008·Blood Cells, Molecules & Diseases·Peter HaviernikKevin D Bunting
Dec 4, 2010·International Journal of Cancer. Journal International Du Cancer·Yu ChenDaiming Fan
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Aug 15, 1997·The Journal of Biological Chemistry·Y E LiuY E Shi

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