Document Detail

Keratinocytes drive melanoma invasion in a reconstructed skin model.
MedLine Citation:
PMID:  20700063     Owner:  NLM     Status:  MEDLINE    
Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling of the extracellular matrix including basement membranes. Here we used a reconstructed skin model to investigate melanoma growth and invasion in vitro. Using this model we show that the dermoepidermal basement membrane prevents the invasion of metastatic melanoma BLM and MV3 cells in the absence of a stratified epidermis. In the reconstructed skin model, matrix metalloproteinase-9, a protease activated early in melanoma development, is secreted by the keratinocytes and subsequently activated by an unknown soluble factor secreted by the melanoma cells. The dynamic interplay between keratinocytes and melanoma cells is further shown by an altered growth pattern of melanoma cells and the finding that a reconstructed epidermis induces invasion. Overall, our findings show that the invasive behavior of melanoma cells is determined by the melanoma cells themselves, but that the interplay between surrounding keratinocytes and the melanoma cells plays an important role in melanoma invasion.
Jeroen W J Van Kilsdonk; Mieke Bergers; Léon C L T Van Kempen; Joost Schalkwijk; Guido W M Swart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Melanoma research     Volume:  20     ISSN:  1473-5636     ISO Abbreviation:  Melanoma Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-09     Completed Date:  2011-01-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  372-80     Citation Subset:  IM    
Department of Biomolecular Chemistry, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
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MeSH Terms
Cell Communication / physiology
Cell Proliferation
Cells, Cultured
Keratinocytes / pathology,  physiology*
Melanoma / pathology*
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Organ Culture Techniques / methods
Skin* / pathology
Skin Neoplasms / pathology*
Skin Physiological Processes
Tissue Engineering / methods
Tissue Scaffolds

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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