MDC-9 (ADAM-9/meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin

MDC-9 is a widely expressed member of the metalloproteinase/disintegrin/cys teine-rich protein family. The disintegrin domain of MDC-9 lacks an RGD mot if but has recently been reported to bind the alpha (6)beta (1) integrin; h owever, it is unclear whether MDC-9 can bind other integrins. In the presen t study myeloma cells, but not lymphoblastoid cells, were shown to bind to immobilised, recombinantly expressed MDC-9 disintegrin domain (A9dis). Bind ing was divalent cation-dependent, being supported by Mn2+ and Ca2+. Adhesi on of myeloma cells to A9dis was completely inhibited by an antibody to the alpha (v)beta (5) integrin but not by antibodies to other subunits. RGD-co ntaining peptides had no effect on binding, suggesting that MDC-9 interacts with alpha (v)beta (5) in an RGD-independent manner. Flow cytometric analy ses demonstrated that myeloma cells, but not lymphoblastoid cells, expresse d alpha (v)beta (5) On the cell membrane. These data indicated that the dis integrin domain of MDC-9 can function as an adhesion molecule by interactin g with an alpha (v)beta (5) integrin. (C) 2001 Academic Press.