Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer

Schmidt,Marianne; Scholz,Claus-Juergen; Polednik,Christine; Roller,Jeanette

doi:10.3892/or.2016.4581

Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer

Authors:
- Marianne Schmidt
- Claus-Juergen Scholz
- Christine Polednik
- Jeanette Roller
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Affiliations: Department of Otorhinolaryngology, University of Würzburg, D-97080 Würzburg, Germany, Interdisciplinary Center for Clinical Research, Microarray Core Unit, University of Würzburg, D-97078 Würzburg, Germany
Published online on: January 21, 2016 https://doi.org/10.3892/or.2016.4581
Pages: 2431-2440

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Abstract

In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually resulting in upregulation following aggregation into 3D structures. Cell lines expressing only low levels of E-cadherin in monolayers produced only loose cell clusters, frequently decreasing E-cadherin expression further upon aggregation. In these cell lines no epidermal growth factor receptor (EGFR) upregulation occurred and proliferation generally decreased in spheroids/aggregates independent of E-cadherin expression. In a second approach a global gene expression analysis of the larynx carcinoma cell line HLaC78 monolayer and the corresponding spheroids was performed. A global upregulation of gene expression in HLaC78 spheroids was related to genes involved in cell adhesion, cell junctions and cytochrome P450-mediated metabolism of xenobiotics. Downregulation was associated with genes controlling cell cycle, DNA-replication and DNA mismatch repair. Analyzing the expression of selected genes of each functional group in monolayer and spheroid cultures of all 12 cell lines revealed evidence for common gene expression shifts in genes controlling cell junctions, cell adhesion, cell cycle and DNA replication as well as genes involved in the cytochrome P450-mediated metabolism of xenobiotics.

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