Sarray Sameh, Berthet Virginie, Calvete Juan J, Secchi Jeannine, Marvaldi Jacques, El-Ayeb Mohamed, Marrakchi Naziha, Luis José
Laboratoire des venins et toxines, Institut Pasteur de Tunis, Tunis, Tunisia.
Lab Invest. 2004 May;84(5):573-81. doi: 10.1038/labinvest.3700088.
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.
整合素家族的黏附受体在肿瘤进展过程中发挥着重要作用,因此是开发新型治疗药物的有趣潜在靶点。蛇毒中含有称为去整合素的整合素 - 配体相互作用的天然抑制剂。它还含有主要作为血小板聚集调节剂而闻名的C型凝集素蛋白。在本研究中,我们证明了从黎凡特蝰蛇毒中分离出的一种新型C型凝集素——黎凡特凝集素(lebectin)具有抗整合素活性。黎凡特凝集素抑制了各种肿瘤细胞系与不同黏附底物的整合素介导的附着。在趋触性试验中,这种C型凝集素还完全阻断了细胞向纤连蛋白的迁移,并阻止肿瘤细胞侵袭纤维蛋白凝胶。此外,黎凡特凝集素被证明是肿瘤细胞增殖的有效抑制剂。尽管本研究中未确定受黎凡特凝集素影响的特定整合素,但整合素α5β1可能参与其中。