| Texto completo | |
| Autor(es): |
Casali, Bruna Carla
;
Baptista, Matheus Pintor
;
Pachane, Bianca Cruz
;
Cortez, Anelise Abreu
;
Altei, Wanessa Fernanda
;
Selistre-de-Araujo, Heloisa Sobreiro
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOCHEMISTRY AND BIOPHYSICS REPORTS; v. 38, p. 7-pg., 2024-03-17. |
| Resumo | |
Breast cancer is a relevant cause of mortality in women and its triple-negative subtype (TNBC) is usually associated with poor prognosis. During tumor progression to metastasis, angiogenesis is triggered by the sprouting of endothelial cells from pre-existing vessels by a dynamic chain of events including VE-cadherin downregulation, actin protrusion, and integrin-mediated adhesion, allowing for migration and proliferation. The binding of tumoral and tumor-associated stromal cells with the extracellular matrix through integrins mediates angiogenic processes and certain integrin subtypes, such as the alpha v beta 3 integrin, are upregulated in hypoxic TNBC models. Integrin alpha v beta 3 inhibition by the high-affinity binding disintegrin DisBa-01 was previously demonstrated to induce anti-tumoral and anti-angiogenic responses in traditional 2D cell assays. Here, we investigate the effects of integrin alpha v beta 3 blockage in endothelial and TNBC cells by DisBa-01 in 3D cultures under two oxygen conditions (1% and 20%). 3D cultures created using non-adhesive micromolds with Matrigel were submitted to migration assay in Boyden chambers and fluorescence analysis. DisBa-01 inhibited cell migration in normoxia and hypoxia in both MDA-MB-231 and HUVEC spheroids. Protein levels of integrin alpha v beta 3 were overexpressed in HUVEC spheroids compared to MDA-MB-231 spheroids. In HUVEC 3D cultures, sprouting assays in collagen type I were decreased in normoxia upon DisBa-01 treatment, and VE-cadherin levels were diminished in HUVEC spheroids in hypoxia and upon DisBa-01 treatment. In conclusion, the blockage of integrin alpha v beta 3 by DisBa-01 inhibits cell migration in 3D culture and interferes with tumor-derived responses in different oxygen settings, implicating its crucial role in angiogenesis and tumor progression. (AU) | |
| Processo FAPESP: | 19/11437-7 - Mecanismos moleculares de ação das integrinas durante a progressão tumoral e o desenvolvimento de metástases: uma abordagem intercelular |
| Beneficiário: | Heloisa Sobreiro Selistre de Araújo |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/01983-4 - Influência de vesículas extracelulares hipóxicas na invasão celular e no microambiente tumoral do Câncer de Mama |
| Beneficiário: | Bianca Cruz Pachane |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |