title: Recombinant disintegrin targets α(v) β(3) integrin and leads to mediator production.
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.
authors.affiliation: Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
authors.forename: Lívia C A
authors.initials: LC
authors.lastname: Ribeiro
authors.affiliation: Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
authors.forename: Lívia C
authors.initials: LC
authors.lastname: Massimino
authors.affiliation: Department of Physiological Sciences São Carlos Federal University São Carlos, São Paulo, Brazil.
authors.forename: Araceli C
authors.initials: AC
authors.lastname: Durante
authors.affiliation: Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Tansini
authors.affiliation: Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Urbaczek
authors.affiliation: Department of Physiological Sciences São Carlos Federal University São Carlos, São Paulo, Brazil.
authors.forename: Heloísa S
authors.initials: HS
authors.lastname: Selistre-de-Araújo
authors.affiliation: Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
authors.forename: Iracilda Z
authors.initials: IZ
authors.lastname: Carlos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D019483:Disintegrins / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D019096:Vitronectin / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D016207:Cytokines; D019483:Disintegrins; D039302:Integrin alphaVbeta3; D011994:Recombinant Proteins; D019096:Vitronectin
keywords: DisBa; HUVEC; IL-8; TGF; VEGF; cancer; endothelial cell; integrin αvβ3; macrophage