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Vol. 13, No. 1, pp. 35-48, January 1, 1999
Molecular Pathology Unit and MGH Cancer Center, Massachusetts
General Hospital, and Department of Pathology, Harvard Medical School,
Boston, Massachusetts 02129 USA
The cell surface hyaluronan receptor CD44 promotes tumor growth and
metastasis by mechanisms that remain poorly understood. We show here
that CD44 associates with a proteolytic form of the matrix
metalloproteinase-9 (MMP-9) on the surface of mouse mammary carcinoma
and human melanoma cells. CD44-associated cell surface MMP-9 promotes
cell-mediated collagen IV degradation in vitro and mediates tumor cell
invasion of G8 myoblast monolayers. Several distinct CD44 isoforms
coprecipitate with MMP-9 and CD44/MMP-9 coclustering is
observed to be dependent on the ability of CD44 to form
hyaluronan-induced aggregates. Disruption of CD44/MMP-9 cluster formation, by overexpression of soluble or truncated cell surface CD44, is shown to inhibit tumor invasiveness in vivo. Our
observations indicate that CD44 serves to anchor MMP-9 on the cell
surface and define a mechanism for CD44-mediated tumor invasion.
[Key Words: CD44; tumor; invasion; MMP-9; cell surface]
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