Lumican inhibits B16F1 melanoma cell lung metastasis.
BACKGROUND
Lumican is a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM) involved in the control of melanoma growth and invasion. The aim of the present study was to analyse the role of lumican in the regulation of the development of lung metastasis.


METHODS
B16F1 melanoma cells stably transfected with lumican expressing plasmid (Lum-B16F1) were injected to syngenic mice. The lung metastasis was compared to mice injected with mock-transfected B16F1 cells (Mock-B16F1). The expression of lumican, cyclin D1, apoptotic markers, vascular endothelium growth factor (VEGF) and Von Willebrand Factor (vWF) within lung metastasis nodules was investigated by immunohistochemistry. In parallel, cells cultured in presence of lumican were assayed for apoptosis and motility.


RESULTS
We observed that the number and the size of lung metastasis nodules were significantly decreased in mice injected with Lum-B16F1 cells in comparison to Mock-B16F1 cells. This was associated with an increase of tumour cell apoptosis within metastasis nodules but the cell proliferation rate remained constant in the two mice groups. In contrast, the VEGF immunostaining and the number of blood vessels within the lung metastasis nodules were decreased in the lumican-expressing tumours. In vitro, a significant decrease of apoptotic markers in wild type B16F1 cells incubated with increasing amounts of lumican core protein was observed. In addition, pseudotubes formation on Matrigel(R) and the migratory capacity of endothelial cells was inhibited by lumican. Altogether, our results indicate that lumican decreases lung metastasis development not only by inducing tumour cell apoptosis but also by inhibiting angiogenesis.
Brezillon
S
S
Laboratoire de Biochimie Médicale et Biologie Moléculaire, CNRS UMR 6237, IFR53 Interactions Cellules-Microenvironnement, Faculté de Médecine, Université de Reims-Champagne-Ardenne, 51095 Reims, France. stephane.brezillon@univ-reims.fr
Zeltz
C
C
Schneider
L
L
Terryn
C
C
Vuillermoz
B
B
Ramont
L
L
Perrau
C
C
Pluot
M
M
Diebold
M D
MD
Radwanska
A
A
Malicka-Blaszkiewicz
M
M
Maquart
F-X
FX
Wegrowski
Y
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007632:Keratan Sulfate / Q000494:pharmacology*; D000071234:Lumican; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D007632:Keratan Sulfate