Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion

The ADAMs (A disintegrin and metalloprotease) com prise a family of membran e-anchored cell surface proteins with a putative role in cell-cell and/or c ell-matrix interactions. By immunostaining, ADAM 12 (meltrin alpha) was up- regulated in several human carcinomas and could be detected along the tumor cell membranes. Because of this intriguing staining pattern, we investigat ed whether human ADAM 12 supports tumor cell adhesion. Using an in vitro as say using recombinant polypeptides expressed in Escherichia coli, we examin ed the ability of individual domains of human ADAM 12 and ADAM 15 to suppor t tumor cell adhesion. We found that the disintegrin-like domain of human A DAM 15 supported adhesion of alpha v beta 3-expressing A375 melanoma cells. In the case of human ADAM 12, however, recombinant polypeptides of the cys teine-rich domain but not the disintegrin-like domain supported cell adhesi on of a panel of carcinoma cell lines. On attachment to recombinant polypep tides from the cysteine-rich domain of human ADAM 12, most tumor cell lines , such as MDA-MB-231 breast carcinoma cells, were rounded and associated wi th numerous actin-containing filopodia and used a cell surface heparan sulf ate proteoglycan to attach. Finally, we demonstrated that authentic full-le ngth human ADAM 12 could bind to heparin Sepharose. Together these results suggest a novel role of the cysteine-rich domain of ADAM 12 - that of suppo rting tumor cell adhesion.