Cloning and characterization of the zebrafish (Danio rerio) aryl hydrocarbon receptor

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.