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The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, Sweden.
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2019 (English)In: Cancer Cell International, ISSN 1475-2867, E-ISSN 1475-2867, Vol. 19, no 16Article in journal (Refereed) Published
Abstract [en]

Background

Head 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.

Methods

The 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.

Results

We 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.

Conclusions

Taken 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.

Place, publisher, year, edition, pages
BioMed Central, 2019. Vol. 19, no 16
Keywords [en]
Cancer stem cells; Drug response; Epithelial–mesenchymal transition; Head and Neck Squamous Cell Carcinoma; Spheroids
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-153947DOI: 10.1186/s12935-019-0733-1ISI: 000455593400001PubMedID: 30651721Scopus ID: 2-s2.0-85059943217OAI: oai:DiVA.org:liu-153947DiVA, id: diva2:1280920
Note

Funding agencies: Korea-Sweden Joint Research Programme; Swedish Cancer Society [2017/301]; County Council of Ostergotland; Research Funds of Linkoping University Hospital; Cancer Foundation of Ostergotland

Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-03-29Bibliographically approved

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