Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion
Abstract
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.
Keywords
Footnotes
-
↵1 Corresponding author.
-
E-MAIL stamenko{at}helix.mhg.harvard.edu; FAX (617) 726-5684.
-
- Received August 5, 1998.
- Accepted November 13, 1998.
- Cold Spring Harbor Laboratory Press