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Recombinant desintegrin DisBa-01 effect in liposome and non-liposome form on macrophages and neoplasic cells: evaluation of cytokine production and pro-angiogenic factors

Abstract

Integrins are non-enzymatic proteins associated with cellular adhesion regulation, allowing a stable anchorage, mobility and migration, besides being able of triggering an intracellular signalization, which may modify cell morphology, migration, survival and proliferation. At cancer sites, integrins may also regulate tumor-associated host cells, which can modify the malignant potential displayed by the whole neoplasia. Alpha-v-beta3 integrin is capable to bind compounds that express RGD motif, especially vitronectin and fibronectin. This integrin is expressed by several human tumors, but it is present in reduced levels or even absent in normal human tissues. This integrin appear to be related to cellular growth control, survival and migration during angiogenesis.alpha-5-beta1 integrin also can connect with RGD motif, showing a particular affinity to fibronectin. It is associated with inflammatory diseases and express well-known proangiogenic functions. It has been demonstrated that molecules able to antagonize these two integrins may express antiangiogenic and antiadherent properties. Recombinant desintegrin DisBa-01 binds to alpha-v-beta3 and alpha-IIb-beta3 integrins and is able to inhibit endothelial cell proliferation and to inhibit cell adhesion to vitronectin. We intend to verify DisBa-01 role as a potential anti-tumoral compound, using its free form as well its lipossomal form, on tumoral cell lineages and to verify its action on cytokine production by culture of macrophages. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO, LIVIA C. A.; MASSIMINO, LIVIA C.; DURANTE, ARACELI C.; TANSINI, ALINE; URBACZEK, ANA C.; SELISTRE-DE-ARAUJO, HELOISA S.; CARLOS, IRACILDA Z.. Recombinant disintegrin targets alpha(v) beta(3) integrin and leads to mediator production. CELL ADHESION & MIGRATION, v. 8, n. 1, p. 60-65, . (11/07798-2, 10/05428-0, 10/01568-2)

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