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Endocrine

, Volume 66, Issue 2, pp 288–300 | Cite as

Establishment and characterization of a new patient-derived anaplastic thyroid cancer cell line (C3948), obtained through fine-needle aspiration cytology

  • Ana T. Pinto
  • Marta Pojo
  • Joana Simões-Pereira
  • Ruben Roque
  • Ana Saramago
  • Lúcia Roque
  • Carmo Martins
  • Saudade André
  • José Cabeçadas
  • Valeriano Leite
  • Branca M. CavacoEmail author
Original Article
  • 95 Downloads

Abstract

Purpose

Anaplastic thyroid cancer (ATC) is among the most aggressive and unresectable tumors, presenting a bad prognosis. A better comprehension of the functional and molecular mechanisms behind the aggressiveness of this cancer, as well as new biomarkers for aggressiveness, prognosis, and response to therapy are required. However, owing to their irresectability, ATC tissue is not always accessible. Here we describe the establishment and characterization of a new patient-derived cell line, obtained from an unresectable ATC through fine-needle aspiration cytology (FNAC).

Methods

The morphology, expression of epithelial and thyroid markers, cytogenetic, mutational and gene expression profiles, doubling time, and drug-resistance profile of the new cell line, designated C3948, were investigated using several methodologies: immunostaining, karyotype analysis, comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), next-generation sequencing (NGS), Sanger sequencing, gene expression microarrays, cell counting, and IC50 determination.

Results

Results indicate that C3948 cell line has a histological phenotype representative of original ATC cells and a completely aberrant karyotype with many chromosomal losses and gains; harbors mutated TP53, STK11, and DIS3L2 genes; presents a gene expression profile similar to C643 ATC commercial cell line, but with some unique alterations; has a doubling time similar to C643; and the IC50 profile for paclitaxel, doxorubicin, and cisplatin is similar to C643, although higher for cisplatin.

Conclusions

These observations are consistent with a typical ATC cell profile, supporting C3948 cell line as a novel preclinical model, and FNAC as a useful approach to better study anaplastic thyroid cancer, including testing of new anticancer therapies.

Keywords

Anaplastic thyroid cancer Tumor cell line Fine-needle aspiration cytology Genetic profile Cytogenetic techniques Molecular biology 

Notes

Acknowledgements

The authors are thankful for the collaboration of the Endocrinology (Dr. Rita Santos) and Pathology Departments from Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). This work was funded by Associação de Endocrinologia Oncológica (AEO), IPOLFG and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundação para a Ciência e Tecnologia/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. M.P. was supported by Núcleo Regional Sul da Liga Portuguesa Contra o Cancro.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12020_2019_2009_MOESM1_ESM.docx (32 kb)
Supporting Information
12020_2019_2009_MOESM2_ESM.xlsx (14.4 mb)
Supporting Tables

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ana T. Pinto
    • 1
  • Marta Pojo
    • 1
  • Joana Simões-Pereira
    • 1
    • 2
    • 3
  • Ruben Roque
    • 4
  • Ana Saramago
    • 1
  • Lúcia Roque
    • 1
  • Carmo Martins
    • 1
  • Saudade André
    • 4
  • José Cabeçadas
    • 4
  • Valeriano Leite
    • 1
    • 2
    • 3
  • Branca M. Cavaco
    • 1
    Email author
  1. 1.Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG) E.P.E., Rua Prof. Lima BastoLisboaPortugal
  2. 2.Serviço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG) E.P.E.LisboaPortugal
  3. 3.Faculdade de Ciências MédicasNova Medical SchoolLisboaPortugal
  4. 4.Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG) E.P.E.Rua Prof. Lima BastoLisboaPortugal

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