Influence of tumour necrosis factor alpha on epithelial-mesenchymal transition of oral cancer cells in co-culture with mesenchymal stromal cells.
Int J Oral Maxillofac Surg
; 49(2): 157-165, 2020 Feb.
Article
em En
| MEDLINE
| ID: mdl-31345665
ABSTRACT
Tumour progression in head and neck squamous cell carcinoma (HNSCC) is influenced by the surrounding stroma and inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). The aim of this study was to test the hypothesis that TNF-α modulates the interactions of HNSCC cell line PCI-13 and bone marrow mesenchymal stromal cells (BMSCs) and influences markers of epithelial-mesenchymal transition (EMT). Following induction with TNF-α, mono- and co-cultures of BMSCs and the established HNSCC cell line PCI-13 were analyzed; protein expression of E-cadherin and vimentin and qRT-PCR expression of Snail, Twist, MMP14, vimentin, E-cadherin, and ß-catenin were examined, and changes in cellular AKT signalling were analyzed. TNF-α induced a significant decrease in E-cadherin (64.5±6.0%, P=0.002) and vimentin (10.4±3.5%, P=0.04) protein expression in co-cultured PCI-13, while qRT-PCR showed a significant increase in ß-catenin (BMSCs P<0.0001; PCI-13 P=0.0005) and Snail (BMSCs P=0.009; PCI-13 P=0.01). TNF-α also resulted in a down-regulation of AKT downstream targets S6 (38.7±20.9%, P=0.01), p70S6 (16.7±12%, P=0.05), RSK1 (23.6±28.8%, P=0.02), and mTOR (27.4±17.5%, P=0.004) in BMSC co-cultures. In summary, while reducing the expression of vimentin and AKT-signalling in PCI-13 and BMSC, respectively, TNF-α introduced an inflammatory-driven tumour-stroma transition, marked by an increased expression of markers of EMT.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
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Carcinoma de Células Escamosas
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Células-Tronco Mesenquimais
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Intervenção Coronária Percutânea
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Neoplasias de Cabeça e Pescoço
Limite:
Humans
Idioma:
En
Revista:
Int J Oral Maxillofac Surg
Assunto da revista:
ODONTOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article