Document Detail

Matrix metalloproteinase-7 activates heparin-binding epidermal growth factor-like growth factor in cutaneous squamous cell carcinoma.
MedLine Citation:
PMID:  20586780     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Tumour-specific expression of matrix metalloproteinase (MMP)-7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB).
OBJECTIVES: To examine the potential role of MMP-7 in shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in RDEB-associated and sporadic SCCs.
METHODS: Tissue microarrays of RDEB-associated SCC (n = 20), non-EB SCC (n = 60) and Bowen disease (n = 28) were immunostained for MMP-7, CD44 variant 3 (CD44v3) and HB-EGF. Shedding of HB-EGF was studied in vitro using two cutaneous SCC cell lines.
RESULTS: Immunohistochemical analysis showed that HB-EGF was absent in tumour cells when MMP-7 and CD44v3 colocalized, and that the absence of HB-EGF was more pronounced in RDEB-associated SCCs than in non-EB SCCs. The loss of HB-EGF in MMP-7-CD44v3 double-positive areas was interpreted to indicate shedding and activation of HB-EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP-7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB-EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells.
CONCLUSIONS: These findings provide evidence for the role of MMP-7 in promoting the growth of cutaneous SCCs by shedding HB-EGF, and identify EGFR signalling as a potential therapeutic target in RDEB-associated SCC and unresectable sporadic cutaneous SCC.
A K Kivisaari; M Kallajoki; R Ala-aho; J A McGrath; J W Bauer; R Königová; M Medvecz; W Beckert; R Grénman; V-M Kähäri
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-02
Journal Detail:
Title:  The British journal of dermatology     Volume:  163     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-03-08     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  726-35     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. BJD © 2010 British Association of Dermatologists.
Department of Dermatology, University of Turku and Turku University Hospital, PO Box 52, 20521 Turku, Finland.
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MeSH Terms
Antigens, CD44 / metabolism
Carcinoma, Squamous Cell / metabolism*,  pathology
Cell Proliferation / drug effects
Dipeptides / pharmacology
Enzyme Activation
Gene Knockdown Techniques
Intercellular Signaling Peptides and Proteins / metabolism*
Matrix Metalloproteinase 7 / physiology*
Matrix Metalloproteinase Inhibitors
Middle Aged
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neoplasm Proteins / metabolism
Protease Inhibitors / pharmacology
RNA, Small Interfering / genetics
Receptor, Epidermal Growth Factor / physiology
Signal Transduction / physiology
Skin Neoplasms / metabolism*,  pathology
Tumor Cells, Cultured
Young Adult
Reg. No./Substance:
0/Antigens, CD44; 0/CD44V3,8-10; 0/Dipeptides; 0/Intercellular Signaling Peptides and Proteins; 0/Matrix Metalloproteinase Inhibitors; 0/N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; 0/Neoplasm Proteins; 0/Protease Inhibitors; 0/RNA, Small Interfering; 149176-25-0/heparin-binding EGF-like growth factor; EC, Epidermal Growth Factor; EC protein, human; EC Protein Kinase 1; EC Protein Kinase 3; EC protein, human; EC Metalloproteinase 7

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