Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC)
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/224789 |
Resumo: | The 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. |
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Montenegro, Cyntia de FreitasCasali, Bruna C.Lino, Rafael L.B.Pachane, Bianca C.Santos, Patty Karina dosHorwitz, Alan RickSelistre-de-Araújo, Heloisa S.Lamers, Marcelo Lazzaron2021-07-29T04:31:40Z20171932-6203http://hdl.handle.net/10183/224789001025757The 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.application/pdfengPLoS ONE. San Francisco. Vol. 12, no. 4 (Apr. 2017), e0176226, 14 f.Neoplasias bucaisPatologia bucalCarcinoma de células escamosasInhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC)Estrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001025757.pdf.txt001025757.pdf.txtExtracted Texttext/plain46685http://www.lume.ufrgs.br/bitstream/10183/224789/2/001025757.pdf.txt61f61ea83adc8c77a8c02705d64c1894MD52ORIGINAL001025757.pdfTexto completo (inglês)application/pdf5841025http://www.lume.ufrgs.br/bitstream/10183/224789/1/001025757.pdfe5762de4739868996112158d97ff89f1MD5110183/2247892023-01-19 06:02:46.736313oai:www.lume.ufrgs.br:10183/224789Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-01-19T08:02:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
title |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
spellingShingle |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) Montenegro, Cyntia de Freitas Neoplasias bucais Patologia bucal Carcinoma de células escamosas |
title_short |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
title_full |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
title_fullStr |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
title_full_unstemmed |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
title_sort |
Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC) |
author |
Montenegro, Cyntia de Freitas |
author_facet |
Montenegro, Cyntia de Freitas Casali, Bruna C. Lino, Rafael L.B. Pachane, Bianca C. Santos, Patty Karina dos Horwitz, Alan Rick Selistre-de-Araújo, Heloisa S. Lamers, Marcelo Lazzaron |
author_role |
author |
author2 |
Casali, Bruna C. Lino, Rafael L.B. Pachane, Bianca C. Santos, Patty Karina dos Horwitz, Alan Rick Selistre-de-Araújo, Heloisa S. Lamers, Marcelo Lazzaron |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Montenegro, Cyntia de Freitas Casali, Bruna C. Lino, Rafael L.B. Pachane, Bianca C. Santos, Patty Karina dos Horwitz, Alan Rick Selistre-de-Araújo, Heloisa S. Lamers, Marcelo Lazzaron |
dc.subject.por.fl_str_mv |
Neoplasias bucais Patologia bucal Carcinoma de células escamosas |
topic |
Neoplasias bucais Patologia bucal Carcinoma de células escamosas |
description |
The 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. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2021-07-29T04:31:40Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/224789 |
dc.identifier.issn.pt_BR.fl_str_mv |
1932-6203 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001025757 |
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1932-6203 001025757 |
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http://hdl.handle.net/10183/224789 |
dc.language.iso.fl_str_mv |
eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
PLoS ONE. San Francisco. Vol. 12, no. 4 (Apr. 2017), e0176226, 14 f. |
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