The small leucine-rich proteoglycan lumican inhibits melanoma progression.
Lumican is a member of the small leucine-rich proteoglycan (SLRP) family. It contributes to the organisation of the collagen network and plays an important role in cell migration and tissue repair. The present study aimed to determine the influence of lumican expression on adhesion, anchorage-dependent and -independent growth, migration, in vitro invasion and in vivo melanoma growth. For that purpose, B16F1 mouse melanoma cells were stably transfected with an expression plasmid containing the complete lumican cDNA. Lumican expression by tumor cells did not change the proliferative activity of mouse melanoma cells in monolayer culture and did not influence either cell adhesion to extracellular matrix gel or type I collagen or cell spreading on these substrates. In contrast, lumican-transfected cells were characterized by a strong reduction of their anchorage-independent proliferation in agarose gel and capacity to invade extracellular matrix gel. After subcutaneous injections of transfected B16F1 cells in syngenic mice, lumican expression significantly decreased subcutaneous tumor formation in vivo, with a concomitant decrease of cyclin D1 expression. Lumican induced and/or increased the apoptosis of B16F1 cells. The results suggest that lumican is involved in the control of melanoma growth and invasion and may be considered, like decorin, as an anti-tumor factor from the extracellular matrix.
Vuillermoz
Boris
B
Laboratory of Biochemistry, CNRS UMR 6198, Faculty of Medicine, F-51095 Reims, France.
Khoruzhenko
Antonina
A
D'Onofrio
Marie-France
MF
Ramont
Laurent
L
Venteo
Lydie
L
Perreau
Corinne
C
Antonicelli
Frank
F
Maquart
François-Xavier
FX
Wegrowski
Yanusz
Y
D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D000071234:Lumican; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014162:Transfection
D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D019938:Cyclin D1; D007632:Keratan Sulfate