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PMID: 9887098 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion.

Genes & development ·Vol. 13 ·No. 1 ·1999-01-01 ·Pages 35-48

Yu Q, Stamenkovic I

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.

MeSH Terms
Animals Collagen/metabolism Collagenases/metabolism Endocytosis/physiology Gene Expression Regulation, Enzymologic/genetics Gene Expression Regulation, Neoplastic/genetics Humans Hyaluronan Receptors/immunology Hyaluronic Acid/metabolism Immunohistochemistry Mammary Neoplasms, Experimental/enzymology,pathology Matrix Metalloproteinase 9 Melanoma/enzymology Mice Neoplasm Invasiveness/physiopathology Protein Binding RNA, Messenger/genetics Transfection/genetics Tumor Cells, Cultured
Chemicals
Hyaluronan Receptors RNA, Messenger Hyaluronic Acid Collagen Collagenases Matrix Metalloproteinase 9
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Yu Q
Molecular Pathology Unit and MGH Cancer Center, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129, USA.
Stamenkovic I
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.1.35
Published
1999-01-01
Pages
35-48
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316376
Subset
IM
Grants
NCI NIH HHS · CA55735 · United States
NIGMS NIH HHS · GM48614 · United States
NIGMS NIH HHS · GM54176 · United States
External Links
PubMed source DOI: 10.1101/gad.13.1.35 PMC Full Text View journal details
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