The coxsackie and adenovirus receptor (CAR) is involved in the epithelial cell tight junction, the downregulated expression of which is observed in different cancer types. In the present study, we examined CAR's role in tumor metastasis using a B16 melanoma and CT26 colon adenocarcinoma model of experimental metastasis. In lung metastasis, the colony number of B16 cells stably expressing CAR (B16CAR) was significantly lower than that of the control CAR-negative B16 cells. B16 and CT26 cells transiently expressing CAR, which were transduced with adenovirus (Ad) vector expressing CAR, also reduced lung metastasis, suggesting that CAR plays a role in the early stage of metastasis. CAR expression significantly decreased the accumulation of B16 cells in the lung after i.v. injection and the migration in vitro. CAR expression reduced expression of a v , a 4 , b 3 and b 1 integrin, which play important roles in attachment to cells or basement membrane. Thus, CAR expression likely acts as a metastatic suppressor. ' 2007 Wiley-Liss, Inc. Key words: coxsackie and adenovirus receptor; metastasis; adenovirus vector; integrinThe tumor cell metastasis represents the primary source of clinical morbidity and mortality in the large majority of solid tumors. A mechanistic understanding of metastasis will help in the development of better therapies and improve patient outcome. Metastasis consists of multiple steps with many factors. The loss of adhesion to cells and extracellular matrix allows malignant cell to leave their origin site, degrade the extracellular matrix, enter either the lymphatics or the bloodstream and finally metastasize.

Gene correction frequency in mouse liver by these oligonucleotides was shown to be less than 1/20000 in our assay with the Muta Mouse system.

Background: Gene targeting in vivo provides a potentially powerful method for gene analysis and gene therapy. In order to sensitively detect and accurately measure designed sequence changes, we have used a transgenic mouse system, MutaMouse, which has been developed for detection of mutation in vivo. It carries bacteriophage lambda genome with lacZ + gene, whose change to lacZnegative allele is detected after in vitro packaging into bacteriophage particles. We have also demonstrated that gene transfer with a replication-defective adenovirus vector can achieve efficient and accurate gene targeting in vitro.