Cadherin‐7 interacts with melanoma inhibitory activity protein and negatively modulates melanoma cell migration

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells, which strongly enhances melanoma cell migration and invasion. Detailed analyses performed by our group showed interaction of MIA with extracellular matrix proteins and integrin α4β1 and α5β1 leading to cellular detachment. In this study, we identified cadherin‐7 as a new MIA‐binding protein using surface‐enhanced laser desorption/ionization‐mass spectrometry technology and co‐immunoprecipitation. Cadherin‐7 is a classical cell–cell adhesion molecule which was shown to be upregulated in malignant melanoma. We demonstrated enhanced expression of cadherin‐7 in primary tumor cells compared to metastatic cells. Upregulation of cadherin‐7 expression in metastatic cell lines but also downregulation of expression in cells derived from primary melanomas resulted in reduced cell migration. In addition, we speculate that MIA/cadherin‐7 interaction may regulate cell–cell adhesion of malignant melanoma cells influencing the migration of the cells. Interestingly, overexpression of cadherin‐7 resulted in a decreased MIA mRNA expression. In addition, MIA effects on cell migration were abrogated in cell clones overexpressing cadherin‐7. In conclusion, these findings suggest that cadherin‐7 regulates the expression and activity of MIA and the migration of melanoma cells playing a role in tumor development of malignant melanoma. (Cancer Sci 2009; 100: 261–268)