Head and neck squamous cancer cells enhance the differentiation of human mesenchymal stem cells to adipogenic and osteogenic linages <em>in vitro</em>

Meyer,Till Jasper; Hackenberg,Stephan; Herrmann,Marietta; Gehrke,Thomas; Steber,Magdalena; Hagen,Rudolf; Kleinsasser,Norbert; Scherzad,Agmal

doi:10.3892/ol.2022.13570

Head and neck squamous cancer cells enhance the differentiation of human mesenchymal stem cells to adipogenic and osteogenic linages in vitro

Authors:
- Till Jasper Meyer
- Stephan Hackenberg
- Marietta Herrmann
- Thomas Gehrke
- Magdalena Steber
- Rudolf Hagen
- Norbert Kleinsasser
- Agmal Scherzad
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Affiliations: Department of Oto‑Rhino‑Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, D‑97080 Würzburg, Germany, IZKF Research Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Würzburg, D‑97070 Würzburg, Germany
Published online on: October 31, 2022 https://doi.org/10.3892/ol.2022.13570
Article Number: 450
Copyright: © Meyer et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human mesenchymal stem cells (hMSC) are multipotent cells with the ability to differentiate into a range of different cell types, including fat, bone, cartilage or muscle. A pro‑tumorigenic effect of hMSC has been previously reported as part of the tumor stroma. In addition, studies have previously revealed the influence of hematopoietic and lymphoid tumors on hMSC differentiation to support their own growth. However, this possible phenomenon has not been explored in solid malignancies. Therefore, the aim of the present study was to investigate the effects of head and neck squamous cell carcinoma (HNSCC) lines Cal27 and HLaC78 on the induction of osteogenic and adipogenic differentiation in hMSCs. Native hMSCs were co‑cultured with Cal27 and HLaC78 cells for 3 weeks. Subsequently, hMSC differentiation was assessed using reverse transcription‑PCR and using Oil Red O and von Kossa staining. Furthermore, the effects of differentiated hMSCs on Cal27 and HLaC78 were examined. For this purpose, hMSCs differentiated into the adipogenic (adipo‑hMSC) and osteogenic (osteo‑hMSC) lineages were co‑cultured with Cal27 and HLaC78. Cell viability, cytokine secretion and activation of STAT3 signaling were measured by cell counting, dot blot assay (42 cytokines with focus on IL‑6) and western blotting (STAT3, phosphorylated STAT3, β‑actin), respectively. Co‑culturing hMSCs with Cal27 and HLaC78 cells resulted in both adipogenic and osteogenic differentiation. In addition, the viability of Cal27 and HLaC78 cells was found to be increased after co‑cultivation with adipo‑hMSCs, compared with that of cells co‑cultured with osteo‑hMSC. According to western blotting results, Cal27 cells incubated with adipo‑hMSCs exhibited increased STAT3 activation, compared with that in cells co‑cultured with native hMSCs and osteo‑hMSCs. IL‑6 concentration in the media of Cal27 and HLaC78 after co‑cultivation with respectively incubation with conditioned media of hMSCs, adipo‑hMSCs and osteo‑hMSCs were also found to be increased compared with that in the media of Cal27 and HLaC78 cells incubated with DMEM. To conclude, HNSCC cell lines Cal27 and HLaC78 induced hMSC differentiation towards the adipogenic and osteogenic lineages in vitro. Furthermore, a proliferative effect of adipo‑hMSCs on Cal27 and HLaC78 cells was revealed with STAT3 activation as a possible mechanism. These results warrant further investigation of the interaction between HNSCC cells and hMSCs, with focus on the mechanism underlying the differentiation of hMSCs.

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