Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/44076 |
Resumo: | National Council for Scientific and Technological Development (CNPq), [Grant No. 308595/2016‐5]. |
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Guimaraes, Vanessa Sousa NazareVidal, Manuela Torres AndionValverde, Ludmila de FaroOliveira, Marbele Guimarães deRocha, Leonardo de Oliveira Siquara daCoelho, Paulo Lucas CerqueiraSoares, Fernando AugustoSouza, Bruno Solano de FreitasBezerra, Daniel PereiraColetta, Ricardo D.Pereira, Thiago AlmeidaSantos, Jean Nunes dosRocha, Clarissa Araújo Gurgel2020-10-20T12:47:11Z2020-10-20T12:47:11Z2020GUIMARAES, Vanessa Sousa Nazare et al. Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization. Journal of Molecular Histology, 2020.1567-2379https://www.arca.fiocruz.br/handle/icict/4407610.1007/s10735-020-09913-5National Council for Scientific and Technological Development (CNPq), [Grant No. 308595/2016‐5].Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.D’Or Institute for Research and Education. Botafo, RJ , Brazil / University of São Paulo. School of Dentistry. Butantã, SP, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil.University of Campinas. School of Dentistry. Piracicaba, SP, Brazil.Stanford University School of Medicine. Institute for Stem Cell Biology and Regenerative Medicine. Stanford, CA, USA.Federal University of Bahia. Salvador, BA, Brazil.Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil / Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil.The purpose of this study was to evaluate the expression of Hedgehog (HH) signaling molecules (SHH and GLI-1) by cancerassociated fibroblasts (CAF) in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to detect molecular HH signaling and CAF-related protein expression, including α-SMA and S100A4, in 70 samples of human OSCC. The colocalization of α-SMA and S100A4 with SHH was also evaluated by double-staining. In vitro study was performed using primary normal oral fibroblast (NOF) and CAF through immunofluorescence and Western Blot for CAF-proteins, SHH, and GLI-1. Forty-five cases (64.28%) were positive for α-SMA exclusively in tumor stroma, and S100A4 was identified in the cytoplasm of CAFs in 94.28% (n = 66) of the cases. With respect to stromal cells, 64 (91.43%) OSCC cases were positive for SHH, and 31 were positive for GLI-1 (44.29%); positive correlations were found between SHH and α-SMA (p < 0.0001, φ = 0.51), as well as between SHH and S100A4 (p = 0.087, φ = 0.94). Protein expression of SHH and GLI-1 was observed in primary CAFs and NOFs. Although SHH was found to be localized in the cellular cytoplasm of both cell types, GLI-1 was present only in the nuclei of CAF. Our results indicate that CAFs are not only potential sources of HH ligands in tumor stroma, but may also respond to HH signaling through nuclear GLI-1 activation. We further observed that elevated SHH expression by OSCC cells was associated with higher CAF density, reinforcing the chemoattractant role played by these molecules.engSpringerCâncer oral ·FibroblastoProteína GLI1 ·Proteína HedgehogOral cancer ·Cancer-associated fibroblast ·GLI1 protein ·Hedgehog proteinHedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localizationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/44076/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGuimaraes, V.S.N. Hedgehog....pdfGuimaraes, V.S.N. Hedgehog....pdfapplication/pdf2960427https://www.arca.fiocruz.br/bitstream/icict/44076/2/Guimaraes%2c%20V.S.N.%20Hedgehog....pdffac445765fabac741fb6c3e16aa93ab4MD52TEXTGuimaraes, V.S.N. Hedgehog....pdf.txtGuimaraes, V.S.N. Hedgehog....pdf.txtExtracted texttext/plain42139https://www.arca.fiocruz.br/bitstream/icict/44076/3/Guimaraes%2c%20V.S.N.%20Hedgehog....pdf.txt0301098018a46bd38df3e05dc4e597bfMD53icict/440762023-03-15 14:34:22.729oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:22Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| title |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| spellingShingle |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization Guimaraes, Vanessa Sousa Nazare Câncer oral · Fibroblasto Proteína GLI1 · Proteína Hedgehog Oral cancer · Cancer-associated fibroblast · GLI1 protein · Hedgehog protein |
| title_short |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| title_full |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| title_fullStr |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| title_full_unstemmed |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| title_sort |
Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization |
| author |
Guimaraes, Vanessa Sousa Nazare |
| author_facet |
Guimaraes, Vanessa Sousa Nazare Vidal, Manuela Torres Andion Valverde, Ludmila de Faro Oliveira, Marbele Guimarães de Rocha, Leonardo de Oliveira Siquara da Coelho, Paulo Lucas Cerqueira Soares, Fernando Augusto Souza, Bruno Solano de Freitas Bezerra, Daniel Pereira Coletta, Ricardo D. Pereira, Thiago Almeida Santos, Jean Nunes dos Rocha, Clarissa Araújo Gurgel |
| author_role |
author |
| author2 |
Vidal, Manuela Torres Andion Valverde, Ludmila de Faro Oliveira, Marbele Guimarães de Rocha, Leonardo de Oliveira Siquara da Coelho, Paulo Lucas Cerqueira Soares, Fernando Augusto Souza, Bruno Solano de Freitas Bezerra, Daniel Pereira Coletta, Ricardo D. Pereira, Thiago Almeida Santos, Jean Nunes dos Rocha, Clarissa Araújo Gurgel |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Guimaraes, Vanessa Sousa Nazare Vidal, Manuela Torres Andion Valverde, Ludmila de Faro Oliveira, Marbele Guimarães de Rocha, Leonardo de Oliveira Siquara da Coelho, Paulo Lucas Cerqueira Soares, Fernando Augusto Souza, Bruno Solano de Freitas Bezerra, Daniel Pereira Coletta, Ricardo D. Pereira, Thiago Almeida Santos, Jean Nunes dos Rocha, Clarissa Araújo Gurgel |
| dc.subject.other.pt_BR.fl_str_mv |
Câncer oral · Fibroblasto Proteína GLI1 · Proteína Hedgehog |
| topic |
Câncer oral · Fibroblasto Proteína GLI1 · Proteína Hedgehog Oral cancer · Cancer-associated fibroblast · GLI1 protein · Hedgehog protein |
| dc.subject.en.pt_BR.fl_str_mv |
Oral cancer · Cancer-associated fibroblast · GLI1 protein · Hedgehog protein |
| description |
National Council for Scientific and Technological Development (CNPq), [Grant No. 308595/2016‐5]. |
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2020 |
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2020-10-20T12:47:11Z |
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2020-10-20T12:47:11Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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GUIMARAES, Vanessa Sousa Nazare et al. Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization. Journal of Molecular Histology, 2020. |
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https://www.arca.fiocruz.br/handle/icict/44076 |
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1567-2379 |
| dc.identifier.doi.none.fl_str_mv |
10.1007/s10735-020-09913-5 |
| identifier_str_mv |
GUIMARAES, Vanessa Sousa Nazare et al. Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization. Journal of Molecular Histology, 2020. 1567-2379 10.1007/s10735-020-09913-5 |
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Springer |
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Springer |
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