Differential display cloning was performed to analyze genes that are differentially expressed in matched primary and metastases-derived human colon carcinoma cell lines. This led to the identification of PMA16, a gene identical to the previously cloned motility-related protein gene (MRP1/CD9). Northern and Western blot analyses of cell lines, as well as immunostaining of tissue sections from the original tumor surgical samples, confirmed that MRP1/CD9 was highly expressed at the primary site, compared to the low levels of expression in metastases. We also demonstrated that primary colon cancer cells displayed a significantly higher migration potential, compared to metastasis-derived cells. Antibodies directed against MRP1/CD9 largely prevented cell migration in vitro, but they did not influence cell adhesion. Thus, differential display cloning has allowed for the identification of MRP1/CD9, a motility-related gene product, which may regulate the metastatic phenotype of human colon cancer.