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
CD44Matrix metalloproteinaseBiologyCell biologyCellCancer researchMetastasisMetalloproteinaseCancerBiochemistry
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Publication Info
- Year
- 1999
- Type
- article
- Volume
- 13
- Issue
- 1
- Pages
- 35-48
- Citations
- 701
- Access
- Closed
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Cite This
Qin Yu,
Ivan Stamenkovic
(1999).
Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion.
Genes & Development
, 13
(1)
, 35-48.
https://doi.org/10.1101/gad.13.1.35
Identifiers
- DOI
- 10.1101/gad.13.1.35