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Séminaire externe 12 juin 2009

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Vendredi 12 juin 2009 à 11 h 00

À l’invitation de Claudine Kieda
« Lumican inhibits lung metastasis » »
Docteur Stéphane Brézillon

Laboratoire de Biochimie Médicale et Biologie Moléculaire
CNRS UMR 6237,
Faculté de Médecine
Université de Reims-Champagne-Ardenne
51095 Reims cedex

Lumican is a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM involved in the control of melanoma growth and invasion (1). 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® 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.