{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Casali BC"],"funding":["FAPESP","Coordenação de Aperfeiçoamento de Pessoal de Nível Superior"],"pagination":["101686"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10957371"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["38"],"pubmed_abstract":["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 α<sub>v</sub>β<sub>3</sub> integrin, are upregulated in hypoxic TNBC models. Integrin α<sub>v</sub>β<sub>3</sub> inhibition by the high-affinity binding disintegrin Dis<i>Ba</i>-01 was previously demonstrated to induce anti-tumoral and anti-angiogenic responses in traditional 2D cell assays. Here, we investigate the effects of integrin α<sub>v</sub>β<sub>3</sub> blockage in endothelial and TNBC cells by Dis<i>Ba</i>-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. Dis<i>Ba</i>-01 inhibited cell migration in normoxia and hypoxia in both MDA-MB-231 and HUVEC spheroids. Protein levels of integrin α<sub>v</sub>β<sub>3</sub> 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 Dis<i>Ba</i>-01 treatment, and VE-cadherin levels were diminished in HUVEC spheroids in hypoxia and upon Dis<i>Ba</i>-01 treatment. In conclusion, the blockage of integrin α<sub>v</sub>β<sub>3</sub> by Dis<i>Ba</i>-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."],"journal":["Biochemistry and biophysics reports"],"pubmed_title":["Blockage of αvβ3 integrin in 3D culture of triple-negative breast cancer and endothelial cells inhibits migration and discourages endothelial-to-mesenchymal plasticity."],"pmcid":["PMC10957371"],"funding_grant_id":["001","2019/11437-7","2021/01983-4"],"pubmed_authors":["Baptista MP","Cortez AA","Casali BC","Selistre-de-Araujo HS","Altei WF","Pachane BC"],"additional_accession":[]},"is_claimable":false,"name":"Blockage of αvβ3 integrin in 3D culture of triple-negative breast cancer and endothelial cells inhibits migration and discourages endothelial-to-mesenchymal plasticity.","description":"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 α<sub>v</sub>β<sub>3</sub> integrin, are upregulated in hypoxic TNBC models. Integrin α<sub>v</sub>β<sub>3</sub> inhibition by the high-affinity binding disintegrin Dis<i>Ba</i>-01 was previously demonstrated to induce anti-tumoral and anti-angiogenic responses in traditional 2D cell assays. Here, we investigate the effects of integrin α<sub>v</sub>β<sub>3</sub> blockage in endothelial and TNBC cells by Dis<i>Ba</i>-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. Dis<i>Ba</i>-01 inhibited cell migration in normoxia and hypoxia in both MDA-MB-231 and HUVEC spheroids. Protein levels of integrin α<sub>v</sub>β<sub>3</sub> 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 Dis<i>Ba</i>-01 treatment, and VE-cadherin levels were diminished in HUVEC spheroids in hypoxia and upon Dis<i>Ba</i>-01 treatment. In conclusion, the blockage of integrin α<sub>v</sub>β<sub>3</sub> by Dis<i>Ba</i>-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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2024-11-08T22:27:50.689Z","creation":"2024-11-08T22:27:50.689Z"},"accession":"S-EPMC10957371","cross_references":{"pubmed":["38524278"],"doi":["10.1016/j.bbrep.2024.101686"]}}