Document Detail

V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling.
MedLine Citation:
PMID:  21078678     Owner:  NLM     Status:  MEDLINE    
Versican is a hyaluronan-binding, extracellular chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The short V3 isoform contains the G1 and G3 terminal domains of versican that may potentially interact directly or indirectly with the hyaluronan receptor CD44 and the EGFR, respectively. We have previously described that overexpression of V3 in MeWo human melanoma cells markedly reduces tumor cell growth in vitro and in vivo. In this study we have investigated the signaling mechanism of V3 by silencing the expression of CD44 in control and V3-expressing melanoma cells. Suppression of CD44 had the same effects on cell proliferation and cell migration than those provoked by V3 expression, suggesting that V3 acts through a CD44-mediated mechanism. Furthermore, CD44-dependent hyaluronan internalization was blocked by V3 expression and CD44 silencing, leading to an accumulation of this glycosaminoglycan in the pericellular matrix and to changes in cell migration on hyaluronan. Furthermore, ERK1/2 and p38 activation after EGF treatment were decreased in V3-expressing cells suggesting that V3 may also interact with the EGFR through its G3 domain. The existence of a EGFR/ErbB2 receptor complex able to interact with CD44 was identified in MeWo melanoma cells. V3 overexpression resulted in a reduced interaction between EGFR/ErbB2 and CD44 in response to EGF treatment. Our results indicate that the V3 isoform of versican interferes with CD44 and the CD44-EGFR/ErbB2 interaction, altering the signaling pathways, such as ERK1/2 and p38 MAPK, that regulate cell proliferation and migration.
Daniel Hernández; Laia Miquel-Serra; María-José Docampo; Anna Marco-Ramell; Jennifer Cabrera; Angels Fabra; Anna Bassols
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-03-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1475-85     Citation Subset:  IM    
Departament de Bioquímica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain.
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MeSH Terms
Antigens, CD44 / genetics,  metabolism*
Cell Adhesion / physiology
Cell Division / physiology
Cell Line, Tumor
Cell Movement / physiology
Hyaluronic Acid / metabolism
Hyaluronoglucosaminidase / metabolism
MAP Kinase Signaling System / physiology*
Melanoma / metabolism*,  pathology
Protein Structure, Tertiary
RNA, Small Interfering
Receptor, Epidermal Growth Factor / genetics,  metabolism*
Skin Neoplasms / metabolism*,  pathology
Versicans / chemistry,  genetics,  metabolism*
Reg. No./Substance:
0/Antigens, CD44; 0/CD44 protein, human; 0/RNA, Small Interfering; 0/VCAN protein, human; 126968-45-4/Versicans; 9004-61-9/Hyaluronic Acid; EC protein, human; EC, Epidermal Growth Factor; EC

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