Influence of tumour necrosis factor alpha on epithelial–mesenchymal transition of oral cancer cells in co-culture with mesenchymal stromal cells. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Böhrnsen, F.; Holzenburg, J.; Godek, F.; Kauffmann, P.; Moser, N.; Schliephake, H.
• Is Part Of: International journal of oral & maxillofacial surgery. Volume 49:Issue 2(2020:Feb.)
• Page Start: 157
• Page End: 165
• Publication Date: 2020-02
• Subjects: TNF-α -- HNSCC -- epithelial–mesenchymal -- transition -- MSC; Mouth -- Surgery -- Periodicals; Maxilla -- Surgery -- Periodicals; Dentistry -- Periodicals; Dentistry, Operative; Oral Surgical Procedures; Surgery, Oral; Dentistry; Maxilla -- Surgery; Mouth -- Surgery; Electronic journals; Periodicals; 617.52059
• DOI: 10.1016/j.ijom.2019.06.001
• Languages: English
• ISSNs: 0901-5027

Abstract

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 β-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 β-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.