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Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines

Gretarsson, Sigurdur LU ; Nygren, Alexander LU ; Rosendahl, Ann H LU ; Mylona, Nektaria ; Kjellén, Elisabeth LU ; Jin, Yuesheng LU ; Paulsson, Kajsa LU ; Borg, Åke LU ; Brun, Eva LU and Tennvall, Jan LU , et al. (2020) In Acta Oto-Laryngologica 140(4). p.337-343
Abstract

Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of... (More)

Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oto-Laryngologica
volume
140
issue
4
pages
7 pages
publisher
Taylor & Francis
external identifiers
  • pmid:31922436
  • scopus:85078602713
ISSN
1651-2251
DOI
10.1080/00016489.2019.1704055
language
English
LU publication?
yes
id
9f092fc8-a452-496f-934f-98278b9ab0e0
date added to LUP
2020-01-27 15:32:25
date last changed
2024-04-03 01:46:26
@article{9f092fc8-a452-496f-934f-98278b9ab0e0,
  abstract     = {{<p>Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.</p>}},
  author       = {{Gretarsson, Sigurdur and Nygren, Alexander and Rosendahl, Ann H and Mylona, Nektaria and Kjellén, Elisabeth and Jin, Yuesheng and Paulsson, Kajsa and Borg, Åke and Brun, Eva and Tennvall, Jan and Bergenfelz, Anders and Greiff, Lennart and Wennerberg, Johan and Ekblad, Lars}},
  issn         = {{1651-2251}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{337--343}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oto-Laryngologica}},
  title        = {{Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines}},
  url          = {{http://dx.doi.org/10.1080/00016489.2019.1704055}},
  doi          = {{10.1080/00016489.2019.1704055}},
  volume       = {{140}},
  year         = {{2020}},
}