ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alpha v beta 3 integrin through an RGD-independent mechanism

ADAM 23 (a disintegrin and metalloproteinase domain)/MDC3 (metalloprotease, disintegrin, and cysteine-rich domain) is a member of the disintegrin fami ly of proteins expressed in fetal and adult brain. Ln this work we show tha t the disintegrin-like domain of ADAM 23 produced in Escherichia coli and i mmobilized on culture dishes promotes attachment of different human cells o f neural origin, such as neuroblastoma cells (NB100 and SH-S(y)5(y)) or ast rocytoma cells (U373 and U87 MG). Analysis ur ADAM 23 binding to integrins revealed a specific interaction with alpha v beta 3, mediated by a short am ino acid sequence present in its putative disintegrin loop. This sequence l acks any RGD motif, which is a common structural determinant supporting alp ha v beta 3-mediated interactions of diverse proteins, including other disi ntegrins. alpha v beta 3 also supported adhesion of HeLa cells transfected with a full-length cDNA for ADAM 23, extending the results obtained with th e recombinant protein containing the disintegrin domain of ADAM 23. On the basis of these results, we propose that ADAM 23, through its disintegrin-li ke domain, may function as an adhesion molecule involved in alpha v beta 3- mediated cell interactions occurring in normal and pathological processes, including progression of malignant tumors from neural origin.