Lebectin, a novel C-type lectin from Macrovipera lebetina venom, inhibits integrin-mediated adhesion, migration and invasion of human tumour cells.
The adhesion receptors of the integrin family play an essential role during tumour progression and thus represent interesting potential targets for the development of new therapeutic agents. The snake venom contains natural inhibitors of integrin-ligand interactions called disintegrins. It also contains C-type lectin proteins mainly known as modulators of platelet aggregation. In this study, we demonstrate that lebectin, a novel C-type lectin isolated from Macrovipera lebetina venom, displayed an anti-integrin activity. Lebectin inhibited the integrin-mediated attachment of various tumour cell lines to different adhesion substrata. The C-type lectin also completely blocked cell migration towards fibronectin in haptotaxis assays and prevented invasion of fibrin gels by tumour cells. In addition, lebectin proved to be a potent inhibitor of tumour cell proliferation. Although the specific integrins affected by lebectin are not identified in this study, the integrin alpha 5 beta 1 might be involved.
Sarray
Sameh
S
Laboratoire des venins et toxines, Institut Pasteur de Tunis, Tunis, Tunisia.
Berthet
Virginie
V
Calvete
Juan J
JJ
Secchi
Jeannine
J
Marvaldi
Jacques
J
El-Ayeb
Mohamed
M
Marrakchi
Naziha
N
Luis
José
J
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors*; D020014:K562 Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D017386:Sequence Homology, Amino Acid; D014757:Viper Venoms / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*
D016023:Integrins; D037181:Lectins, C-Type; D014757:Viper Venoms