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) Supports Tumor Cell Adhesion
From the Institute of Molecular Pathology, University of Copenhagen, Copenhagen, Denmark
The ADAMs (A disintegrin and metalloprotease) comprise a family of
membrane-anchored cell surface proteins with a putative role in
cell-cell and/or cell-matrix interactions. By immunostaining,
ADAM 12 (meltrin 
) was up-regulated in several human carcinomas and
could be detected along the tumor cell membranes. Because of this
intriguing staining pattern, we investigated whether human ADAM
12 supports tumor cell adhesion. Using an in vitro assay
using recombinant polypeptides expressed in Escherichia
coli, we examined the ability of individual domains of
human ADAM 12 and ADAM 15 to support tumor cell adhesion. We found that
the disintegrin-like domain of human ADAM 15 supported adhesion of
vß3-expressing A375 melanoma cells. In the case of human ADAM
12, however, recombinant polypeptides of the
cysteine-rich domain but not the disintegrin-like domain supported cell
adhesion of a panel of carcinoma cell lines. On attachment to
recombinant polypeptides 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 with numerous
actin-containing filopodia and used a cell surface heparan sulfate
proteoglycan to attach. Finally, we demonstrated that authentic
full-length 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 supporting tumor cell adhesion.
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