Document Detail

4-Methylumbelliferone inhibits tumour cell growth and the activation of stromal hyaluronan synthesis by melanoma cell-derived factors.
MedLine Citation:
PMID:  20163414     Owner:  NLM     Status:  In-Data-Review    
Background  There is a close correlation between tumour progression and hyaluronan production, either by tumour cells or by stromal cells that are stimulated by tumour-derived factors. Inhibition of tumour stimulation of fibroblast hyaluronan may suppress tumour growth and invasion. Objectives  To examine the effect of the hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) on the growth of and hyaluronan synthesis by fibroblasts and C8161 and MV3 melanoma cell lines, invasion, and inhibition of tumour cell-derived factor activation of fibroblasts. Methods  Effects of 4-MU on growth and hyaluronan synthesis by fibroblasts and melanoma cells were examined in monolayer culture and fibroblast-contracted collagen lattices, and their effects on the growth and invasion of tumour cells into collagen lattices were also studied. Results  4-MU caused a dose-dependent growth inhibition of fibroblast and melanoma cells with maximum inhibition at 0·5 mmol L(-1) 4-MU. At this dose, 4-MU inhibited (3) H-glucosamine incorporation into fibroblast glycosaminoglycans by 52%, and hyaluronan synthesis by 64%. The relative inhibition was more pronounced when fibroblasts were stimulated with C8161 melanoma cell-conditioned medium. 4-MU reduced the level of hyaluronan in fibroblast-contracted collagen lattices, and inhibited both the growth on and invasion into the lattices by melanoma cells. This growth inhibition appears to be predominantly independent of inhibition of hyaluronan synthesis. The effect on growth inhibition was reversible, and 4-MU had no effect on apoptosis. Conclusions  4-MU is a potent inhibitor of hyaluronan synthesis, induction of stromal hyaluronan accumulation by tumour cells, and fibroblast and melanoma cell proliferation, and results suggest that 4-MU may have potential as a tumour cell anti-invasive and antiproliferative agent.
M Edward; J A Quinn; S M Pasonen-Seppänen; B A McCann; R H Tammi
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Publication Detail:
Type:  Journal Article     Date:  2010-02-15
Journal Detail:
Title:  The British journal of dermatology     Volume:  162     ISSN:  1365-2133     ISO Abbreviation:  Br. J. Dermatol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2011-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1224-32     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.
Section of Dermatology, Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, The Robertson Building, University of Glasgow, Glasgow G12 8QQ, U.K. Department of Anatomy, Institute of Biomedicine, University of Eastern Finland, POB 1627, 70211 Kuopio, Finland.
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