Cédric Zeltz

Publications (2)7.12 Total impact

• Article: Lumican inhibits cell migration through α2β1 integrin.

  Cédric Zeltz, Stéphane Brézillon, Jarmo Käpylä, Johannes A Eble, Hélène Bobichon, Christine Terryn, Corinne Perreau, Clemens M Franz, Jyrki Heino, François-Xavier Maquart, Yanusz Wegrowski
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  ABSTRACT: Lumican, an extracellular matrix protein of the small leucine-rich proteoglycan family, has been shown to impede melanoma progression by inhibiting cell migration. In the present study, we show that lumican targets α2β1 integrin thereby inhibiting cell migration. A375 melanoma cells were transfected with siRNA directed against the α2 integrin subunit. Compared to A375 control cells, the anti-migratory effect of lumican was abrogated on transfected A375 cells. Moreover, lumican inhibited the chemotactic migration of Chinese hamster ovary (CHO) cells stably transfected with α2 integrin subunit (CHO-A2) but not that of wild-type CHO cells (CHO-WT) lacking this subunit. In contrast to CHO-WT cells, we observed in time-lapse microscopy a decrease of CHO-A2 cell migration speed in presence of lumican. Focal adhesion kinase phosphorylated at tyrosine-397 (pFAK) and total FAK were analysed in CHO-WT and CHO-A2 cells. A significant decrease of the ratio pFAK/FAK was shown in presence of recombinant human lumican. Using solid phase assays, a direct binding between lumican and the α2β1 integrin was demonstrated. This interaction did not involve the glycan moiety of lumican and was cation independent. Lumican was also able to bind the activated I domain of the α2 integrin subunit with a K(d)≥200nM. In conclusion, we demonstrated for the first time that the inhibition of cell migration by lumican depends on a direct binding between the core protein of lumican and the α2β1 integrin.
  Experimental Cell Research 10/2010; 316(17):2922-31. · 3.58 Impact Factor
• Article: Lumcorin: a leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration.

  Cédric Zeltz, Stéphane Brézillon, Corinne Perreau, Laurent Ramont, François-Xavier Maquart, Yanusz Wegrowski
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  ABSTRACT: We previously showed that lumican decreases melanoma progression. The aim of the present study was to determine the active sequence of the lumican core protein responsible for the inhibition of melanoma cell migration. Using different recombinant and synthetic peptides derived from lumican, we localized an active site in the leucine-rich repeat 9 domain of the lumican core protein. We propose the name lumcorin (fragment of lumican core protein) for the active peptide derived from this site. Lumcorin was able to inhibit melanoma cell migration in vitro.
  FEBS letters 09/2009; 583(18):3027-32. · 3.54 Impact Factor