Document Detail

Melanoma invasion in reconstructed human skin is influenced by skin cells--investigation of the role of proteolytic enzymes.
MedLine Citation:
PMID:  14713103     Owner:  NLM     Status:  MEDLINE    
Melanoma invasion is a complex multi stage process involving changes to the cell/extracellular matrix (ECM) and cell/cell interactions. We have previously shown using an in vitro model of reconstructed human skin (consisting of human dermis with a basement membrane [BM] and populated with human skin cells) that some melanoma cells (HBL cell line) invade more actively in the presence of adjacent normal skin cells. The aim of the present study was to further investigate the relationship between melanoma cells, skin cells and ECM proteins during melanoma cell invasion through reconstructed skin, extending this to a study of three melanoma cell lines. We also examined whether such cell/cell induced invasion is due to increased expression and activation of matrix-metalloproteinase-2 (MMP-2) and MMP-9, or due to increases in general protease activity for keratinocytes, fibroblasts or melanoma lines. Addition of skin cells dramatically altered the invasive behaviour of the three metastatic melanoma cell lines (HBL, C8161 and A375SM) used; they increased the invasive ability of HBLs which were unable to invade on their own; they potentiated the invasion of C8161 cells which were invasive in their own right, but reduced the invasion of A375-SM cells which were aggressive invaders in the absence of skin cells. Latent forms of MMP-2, and MMP-9, were clearly expressed by the normal skin cells whereas all three melanoma lines weakly expressed these proteases. Fibroblast and keratinocyte MMPs were activated specifically by culture on type I collagen and on dermis which retained an intact basement membrane. These findings demonstrate that while there is an active communication between melanoma cells and adjacent skin cells, the invasive process is dictated by the melanoma cells and not the skin cells. However, activation of skin cell derived MMPs may play an important role in facilitating invasion by particular melanoma phenotypes.
Paula Eves; Efthymia Katerinaki; Claire Simpson; Christopher Layton; Rebecca Dawson; Gareth Evans; Sheila Mac Neil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  20     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2003  
Date Detail:
Created Date:  2004-01-09     Completed Date:  2004-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  685-700     Citation Subset:  IM    
Skin Biology Group, Division of Clinical Sciences (North), University of Sheffield, Northern General Hospital, Sheffield, UK.
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MeSH Terms
Cell Communication
Cell Culture Techniques
Cell Line
Coculture Techniques
Fibroblasts / physiology
Keratinocytes / physiology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Matrix Metalloproteinases / metabolism*
Neoplasm Invasiveness*
Peptide Hydrolases / metabolism*
Serine Endopeptidases / metabolism*
Skin Neoplasms / pathology*
Reg. No./Substance:
EC 3.4.-/Peptide Hydrolases; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2; EC Metalloproteinase 9

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