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dc.contributor.authorMontenegro, Cyntia de Freitaspt_BR
dc.contributor.authorCasali, Bruna C.pt_BR
dc.contributor.authorLino, Rafael L.B.pt_BR
dc.contributor.authorPachane, Bianca C.pt_BR
dc.contributor.authorSantos, Patty Karina dospt_BR
dc.contributor.authorHorwitz, Alan Rickpt_BR
dc.contributor.authorSelistre-de-Araújo, Heloisa S.pt_BR
dc.contributor.authorLamers, Marcelo Lazzaronpt_BR
dc.date.accessioned2021-07-29T04:31:40Zpt_BR
dc.date.issued2017pt_BR
dc.identifier.issn1932-6203pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/224789pt_BR
dc.description.abstractThe connective tissue formed by extracellular matrix (ECM) rich in fibronectin and collagen consists a barrier that cancer cells have to overpass to reach blood vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by αvβ3 and α5β1 integrins through an RGD motif present in this ECM protein, thus making these receptors key targets for cell migration studies. Here we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of human fibroblasts (BJ) and oral squamous cancer cells (OSCC, SCC25) on a fibronectin-rich environment. Time-lapse images were acquired on fibronectin-coated glassbottomed dishes. Migration speed and directionality analysis indicated that OSCC cells, but not fibroblasts, showed significant decrease in both parameters in the presence of DisBa-01 (1μM and 2μM). Integrin expression levels of the α5, αv and β3 subunits were similar in both cell lines, while β1 subunit is present in lower levels on the cancer cells. Next, we examined whether the effects of DisBa-01 were related to changes in adhesion properties by using paxillin immunostaining and total internal reflection fluorescence TIRF microscopy. OSCCs in the presence of DisBa-01 showed increased adhesion sizes and number of maturing adhesion. The same parameters were analyzed usingβ3-GFP overexpressing cells and showed that β3 overexpression restored cell migration velocity and the number of maturing adhesion that were altered by DisBa-01. Surface plasmon resonance analysis showed that DisBa-01 has 100x higher affinity for αvβ3 integrin than forα5β1 integrin. In conclusion, our results suggest that the αvβ3 integrin is the main receptor involved in cell directionality and its blockage may be an interesting alternative against metastasis.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofPLoS ONE. San Francisco. Vol. 12, no. 4 (Apr. 2017), e0176226, 14 p.pt_BR
dc.rightsOpen Accessen
dc.subjectNeoplasias bucaispt_BR
dc.subjectPatologia bucalpt_BR
dc.subjectCarcinoma de células escamosaspt_BR
dc.titleInhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC)pt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001025757pt_BR
dc.type.originEstrangeiropt_BR


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