Abstract
BackgroundHead and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies. Therefore searching for predictive markers and new targets for treatment in clinically relevant in vitro tumor models is essential. Five HNSCC-derived cell lines were used to assess the effect of 3D culturing compared to 2D monolayers in terms of cell proliferation, response to anti-cancer therapy as well as expression of EMT and CSC genes.MethodsThe viability and proliferation capacity of HNSCC cells as well as induction of apoptosis in tumor spheroids cells after treatment was assessed by MTT assay, crystal violet- and TUNEL assay respectively. Expression of EMT and CSC markers was analyzed on mRNA (RT-qPCR) and protein (Western blot) level.ResultsWe showed that HNSCC cells from different tumors formed spheroids that differed in size and density in regard to EMT-associated protein expression and culturing time. In all spheroids, an up regulation of CDH1, NANOG and SOX2 was observed in comparison to 2D but changes in the expression of EGFR and EMT markers varied among the cell lines. Moreover, most HNSCC cells grown in 3D showed decreased sensitivity to cisplatin and cetuximab (anti-EGFR) treatment.ConclusionsTaken together, our study points at notable differences between these two cellular systems in terms of EMT-associated gene expression profile and drug response. As the 3D cell cultures imitate the in vivo behaviour of neoplastic cells within the tumor, our study suggest that 3D culture model is superior to 2D monolayers in the search for new therapeutic targets.
Highlights
Head and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies
Cell death was analyzed with a TUNEL assay but only a low number of apoptotic cells was found in the analyzed tumor spheroids (Additional file 1: Figure S1)
We have previously shown that the LK0855 HNSCC cell line with a lower expression of epidermal growth factor receptor (EGFR) than normal oral keratinocytes, shows an increased proliferation after exposure to cetuximab compared to untreated controls [23]
Summary
Head and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies. Five HNSCC-derived cell lines were used to assess the effect of 3D culturing compared to 2D monolayers in terms of cell proliferation, response to anti-cancer therapy as well as expression of EMT and CSC genes. Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide with over half a million new cases annually. The growing research interest in 3D models of different tumor types is focused on assessing the effects of chemo- and/or radiotherapy, studying tumor metastasis, angiogenesis and cancer cell differentiation, apoptosis as well as epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) biology [6, 7]
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