In our previous studies we showed that motility related protein 1 (MRP-1) is a glycoprotein recognized by mAb M31-15, and that the sequence of MRP-1 is identical to that of CD9, a WBC differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured nonhematopoietic cells suppresses cell motility. The extent of suppression is directly related to the level of MRP-1/CD9 expression. In addition, the metastatic potential of MRP-1/CD9-transfected melanoma BL6 cells is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated MRP-1/CD9 expression in 143 invasive ductal carcinomas of the breast. Of 97 patients with MRP-1/CD9-positive tumors, only 36 (37.1%) had lymph node involvement. In contrast, 21 of 39 (53.8%) patients whose tumors had reduced MRP-1/CD9 immunoreactivity and 5 of 7 patients whose primary carcinomas were not stained by the anti-MRP-1/CD9 MAb had lymph node metastases. The comparison of protein expression by 62 primary tumors and their respective metastatic lymph nodes revealed that in almost 50% of the cases, the latter had lower MRP-1/CD9 levels than the former. Moreover, reverse transcriptase-PCR-based analysis disclosed that MRP-1/CD9 gene expression in the metastatic lymph nodes of 17 of 32 patients was strikingly lower than in the primary invasive ductal carcinomas. Gene overexpression was not observed in any of the samples studied. Our data suggest that low MRP-1/CD9 expression may be associated with the metastatic potential of certain human tumors.