Ameloblastoma pathogenesis: WNT signaling and associated cell adhesion molecules

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16170%2F19%3A43877346" target="_blank" >RIV/62157124:16170/19:43877346 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Ameloblastoma pathogenesis: WNT signaling and associated cell adhesion molecules

Popis výsledku v původním jazyce

Ameloblastoma is the most common odontogenic tumor in humans. It is usually benign but can in some cases invade local structures including bones. Recurrence following surgical treatment is very common. Here, we investigated the role of WNT signaling pathway in pathogenesis of ameloblastoma with focus on Frizzled6 (FZD6), one of receptors playing a role in determining the planar cell polarity and WNT related cell-cell adhesion molecules. In human embryos, strong expression of WNT receptor FZD6 was found in the dental lamina and epithelial dental remnants, which are known to contribute to ameloblastoma initiation. Comparison to ameloblastoma tissues revealed a distinct expression pattern of FZD6 in its benign and malignant forms with a robust expression in the central areas of the epithelial islets. To analyze differences in the expression of genes encoding canonical and non-canonical WNT pathway members, we performed a detailed PCR array analysis on healthy gingivae, benign and malignant form of ameloblastomas. Compared to healthy gingivae, the most downregulated WNT ligands in ameloblastoma were WNT4, WNT6, and WNT8a. Some distinct differences between the malignant and benign form were also observed, including downregulation of the WNT7b expression in the malignant tissue. Moreover, downregulation of beta-catenin expression was accompanied by an altered expression of membrane proteins; moreover, beta-catenin associated adhesion molecules such as DSC2, DSP or JUP were downregulated in patient tissues. Instant response of cells on altered WNT signaling changes tested on primary cell cultures confirmed the effect of WNT inhibition on the downregulation of genes associated with cell adhesions. In conclusion, our study provided a deeper insight into the gene expression profile of WNT pathway members in the benign and malignant forms of ameloblastoma, opening up new avenues, which should be tested for potential prediction of future cell behavior in this neoplasm.

Název v anglickém jazyce

Ameloblastoma pathogenesis: WNT signaling and associated cell adhesion molecules

Popis výsledku anglicky

Ameloblastoma is the most common odontogenic tumor in humans. It is usually benign but can in some cases invade local structures including bones. Recurrence following surgical treatment is very common. Here, we investigated the role of WNT signaling pathway in pathogenesis of ameloblastoma with focus on Frizzled6 (FZD6), one of receptors playing a role in determining the planar cell polarity and WNT related cell-cell adhesion molecules. In human embryos, strong expression of WNT receptor FZD6 was found in the dental lamina and epithelial dental remnants, which are known to contribute to ameloblastoma initiation. Comparison to ameloblastoma tissues revealed a distinct expression pattern of FZD6 in its benign and malignant forms with a robust expression in the central areas of the epithelial islets. To analyze differences in the expression of genes encoding canonical and non-canonical WNT pathway members, we performed a detailed PCR array analysis on healthy gingivae, benign and malignant form of ameloblastomas. Compared to healthy gingivae, the most downregulated WNT ligands in ameloblastoma were WNT4, WNT6, and WNT8a. Some distinct differences between the malignant and benign form were also observed, including downregulation of the WNT7b expression in the malignant tissue. Moreover, downregulation of beta-catenin expression was accompanied by an altered expression of membrane proteins; moreover, beta-catenin associated adhesion molecules such as DSC2, DSP or JUP were downregulated in patient tissues. Instant response of cells on altered WNT signaling changes tested on primary cell cultures confirmed the effect of WNT inhibition on the downregulation of genes associated with cell adhesions. In conclusion, our study provided a deeper insight into the gene expression profile of WNT pathway members in the benign and malignant forms of ameloblastoma, opening up new avenues, which should be tested for potential prediction of future cell behavior in this neoplasm.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30204 - Oncology

Projekt

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Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů