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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 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

Melissaridou, Styliani; Wiechec, Emilia; Magan, Mustafa; Jain, Mayur Vilas LU ; Chung, Man Ki; Farnebo, Lovisa and Roberg, Karin (2019) In Cancer Cell International 19(1).
Abstract

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)... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer stem cells, Drug response, Epithelial-mesenchymal transition, Head and Neck Squamous Cell Carcinoma, Spheroids
in
Cancer Cell International
volume
19
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85059943217
ISSN
1475-2867
DOI
10.1186/s12935-019-0733-1
language
English
LU publication?
yes
id
b83fa794-b041-4f26-b173-56292e05ffa6
date added to LUP
2019-01-23 12:12:23
date last changed
2019-02-20 11:44:04
@article{b83fa794-b041-4f26-b173-56292e05ffa6,
  abstract     = {<p>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.</p>},
  articleno    = {16},
  author       = {Melissaridou, Styliani and Wiechec, Emilia and Magan, Mustafa and Jain, Mayur Vilas and Chung, Man Ki and Farnebo, Lovisa and Roberg, Karin},
  issn         = {1475-2867},
  keyword      = {Cancer stem cells,Drug response,Epithelial-mesenchymal transition,Head and Neck Squamous Cell Carcinoma,Spheroids},
  language     = {eng},
  month        = {01},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Cancer Cell International},
  title        = {The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis},
  url          = {http://dx.doi.org/10.1186/s12935-019-0733-1},
  volume       = {19},
  year         = {2019},
}