Evaluation of spheroid head and neck squamous cell carcinoma cell models in comparison to monolayer cultures

Abstract

Abstract. Two-dimensional (2D) monolayer cell culture models are the most common method used to investigate tumor cells in vitro. In the few last decades, a multicellular spheroid model has gained attention due to its adjacency to tumors in vivo. The aim of the present study was to investigate immunohistochemical differences between these two cell culture systems. The FaDu, CAL27 and SCC25 head and neck squamous cell carcinoma (HNSCC) cell lines were seeded out in monolayer and multicellular spheroids. The FaDu and SCC25 cells were treated with increasing doses of cisplatin and irradiation. CAL27 cells were not used in theproliferation experiments, since the spheroids of CAL27 cells were not able to process the reagent in CCK-8 assays. Furthermore, they were stained to present alterations of the following antigens: Ki-67, vascular endothelial growth factor receptor, epithelial growth factor and survivin. Differences in growth rates and expression patterns were detected in certain HNSCC cell lines. The proliferation rates showed a significant divergence of cells grown in the three-dimensional model compared with cells grown in the 2D model. Overall, multicellular spheroids are a promising method to reproduce the immunohistochemical aspects and characteristics of tumor cells, and may show different response rates to therapeutic options.

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer

“…Therefore, predicting clinical response of new agents tested in 2D cellular assays is limited (32). Although 3D cell culture models are commonly seen to be superior to monolayer cultures as a more reliable drug screening tool, there are only a few studies that deal with spheroids in head and neck cancers (27,33,(52)(53)(54).…”

“…Radiation resistance has also been linked to spheroid models in the past. Kadletz et al could not detect any radiationrelated cytotoxicity for a variation of dosages in different HNSCC cell lines (52). However, sensitivity and resistance to irradiation is mainly influenced by effectiveness of DNA repair, apoptosis, oxygen supply and cell-cell contacts, features that, in spheroid cell culture, are similar to tumors in vivo (29,65,66).…”

Impact of spheroid culture on molecular and functional characteristics of bladder cancer cell lines

“…Multicellular spheroids (MCSs) developed in 3D culture are believed to more closely mimic solid tumors with respect to cell-cell interactions, hypoxia, drug penetration, and nutrition gradients, which are irreproducible in conventional two-dimensional (2D) cell culture (1,2). MCSs generated from cancer cell lines alter their molecular phenotypes in various types of cancer, including ovarian, colon, prostate, head and neck, endometrial, and lung (3)(4)(5)(6)(7)(8)(9)(10)(11). Along with the molecular phenotypic changes, functional properties in 3D culture, e.g.…”

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

“…Cisplatin Breast cancer EMT-6 [24] Endometrial cancer Ishikawa [25] RL95-2 [25] KLE [25] Hypopharyngeal cancer FaDu [96] Ovarian cancer OVCAR8 [97] Oral cancer SCC25 [96] CAL27 [96] Chlorimipramine Glioma C6 [98] Cyclophosphamide Breast cancer EMT-6 [24] Diclofenac Liver tissue Hepatocytes obtained from patient [10] Hepatoma C3A [68] Docetaxel Cervical cancer HeLa [99] Colon cancer HT29 [99] Doxorubicin Cervical cancer HeLa [70] Endometrial cancer Ishikawa [25] RL95-2 [25] KLE [25] Hepatoma C3A [68] Huh7 [100] Lung cancer A549 [101] E-combretastatin A4 Melanoma C8161 [102] Breast cancer MDA 231 [102] (Continued) [26] PC3 [26] Fialuridine Liver tissue Hepatocytes obtained from patient [10] Fialuridine Hepatoma C3A [68] Gant61…”