1. Recombinant disintegrin targets α(v) β(3) integrin and leads to mediator production.
- Author
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Ribeiro LC, Massimino LC, Durante AC, Tansini A, Urbaczek AC, Selistre-de-Araújo HS, and Carlos IZ
- Subjects
- Apoptosis drug effects, Cell Adhesion, Cell Survival drug effects, Cells, Cultured, Drug Screening Assays, Antitumor, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells physiology, Humans, Recombinant Proteins pharmacology, Vitronectin metabolism, Angiogenesis Inhibitors pharmacology, Cytokines biosynthesis, Disintegrins pharmacology, Integrin alphaVbeta3 metabolism
- Abstract
Integrin αvβ3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvβ3, thereby significantly inhibiting adhesion and generating in vivo anti-metastatic ability. However, its function in mediator production is not clear. Here, we observed that the mediators VEGF-A, IL-8, and TGF-β are not produced by human umbilical vein endothelial cells (HUVEC cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of TGF-β, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also showed an enhancement of apoptosis after losing adherence when exposed to disintegrin, which is a characteristic of anoikis. We propose that disintegrin DisBa-01 could be used to modulate integrin αvβ3 functions.
- Published
- 2014
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