TY - JOUR
T1 - Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines
AU - Gretarsson, Sigurdur
AU - Nygren, Alexander
AU - Rosendahl, Ann H
AU - Mylona, Nektaria
AU - Kjellén, Elisabeth
AU - Jin, Yuesheng
AU - Paulsson, Kajsa
AU - Borg, Åke
AU - Brun, Eva
AU - Tennvall, Jan
AU - Bergenfelz, Anders
AU - Greiff, Lennart
AU - Wennerberg, Johan
AU - Ekblad, Lars
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - https://scopus.com/record/display.uri?eid=2-s2.0-85078602713&origin=inward&txGid
U2 - 10.1080/00016489.2019.1704055
DO - 10.1080/00016489.2019.1704055
M3 - Article
C2 - 31922436
SN - 1651-2251
VL - 140
SP - 337
EP - 343
JO - Acta Oto-Laryngologica
JF - Acta Oto-Laryngologica
IS - 4
ER -