| Author | Guimaraes, Vanessa Sousa Nazare | |
| Author | Vidal, Manuela Torres Andion | |
| Author | Valverde, Ludmila de Faro | |
| Author | Oliveira, Marbele Guimarães de | |
| Author | Rocha, Leonardo de Oliveira Siquara da | |
| Author | Coelho, Paulo Lucas Cerqueira | |
| Author | Soares, Fernando Augusto | |
| Author | Souza, Bruno Solano de Freitas | |
| Author | Bezerra, Daniel Pereira | |
| Author | Coletta, Ricardo D. | |
| Author | Pereira, Thiago Almeida | |
| Author | Santos, Jean Nunes dos | |
| Author | Rocha, Clarissa Araújo Gurgel | |
| Access date | 2020-10-20T12:47:11Z | |
| Available date | 2020-10-20T12:47:11Z | |
| Document date | 2020 | |
| Citation | 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. | pt_BR |
| ISSN | 1567-2379 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/44076 | |
| Sponsorship | National Council for Scientific and Technological
Development (CNPq), [Grant No. 308595/2016‐5]. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Springer | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Câncer oral · | pt_BR |
| Subject in Portuguese | Fibroblasto | pt_BR |
| Subject in Portuguese | Proteína GLI1 · | pt_BR |
| Subject in Portuguese | Proteína Hedgehog | pt_BR |
| Title | Hedgehog pathway activation in oral squamous cell carcinoma: cancer‑associated fibroblasts exhibit nuclear GLI‑1 localization | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1007/s10735-020-09913-5 | |
| Abstract | 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | D’Or Institute for Research and Education. Botafo, RJ , Brazil / University of São Paulo. School of Dentistry. Butantã, SP, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | University of Campinas. School of Dentistry. Piracicaba, SP, Brazil. | pt_BR |
| Affilliation | Stanford University School of Medicine. Institute for Stem Cell Biology and Regenerative Medicine. Stanford, CA, USA. | pt_BR |
| Affilliation | Federal University of Bahia. Salvador, BA, Brazil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Subject | Oral cancer · | pt_BR |
| Subject | Cancer-associated fibroblast · | pt_BR |
| Subject | GLI1 protein · | pt_BR |
| Subject | Hedgehog protein | pt_BR |
