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In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil

MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-u...

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Autores principales: Virgone-Carlotta, Angélique, Lemasson, Manon, Mertani, Hichem C., Diaz, Jean-Jacques, Monnier, Sylvain, Dehoux, Thomas, Delanoë-Ayari, Hélène, Rivière, Charlotte, Rieu, Jean-Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687732/
https://www.ncbi.nlm.nih.gov/pubmed/29141026
http://dx.doi.org/10.1371/journal.pone.0188100
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author Virgone-Carlotta, Angélique
Lemasson, Manon
Mertani, Hichem C.
Diaz, Jean-Jacques
Monnier, Sylvain
Dehoux, Thomas
Delanoë-Ayari, Hélène
Rivière, Charlotte
Rieu, Jean-Paul
author_facet Virgone-Carlotta, Angélique
Lemasson, Manon
Mertani, Hichem C.
Diaz, Jean-Jacques
Monnier, Sylvain
Dehoux, Thomas
Delanoë-Ayari, Hélène
Rivière, Charlotte
Rieu, Jean-Paul
author_sort Virgone-Carlotta, Angélique
collection PubMed
description MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-up of MCTS with simple and robust readouts to evaluate drug efficacy is still missing. Here, we evaluate the chemotherapeutic drug 5-Fluorouracil (5-FU) response on the growth and integrity of MCTS two days after treatment of MCTS and for three colorectal carcinoma cell lines with different cohesive properties (HT29, HCT116 and SW480). We found different sensitivity to 5-FU for the three CRC cell lines, ranging from high (SW480), intermediate (HCT116) and low (HT29) and the same hierarchy of CRC cell lines sensitivity is conserved in 2D. We also evidence that 5-FU has a strong impact on spheroid cohesion, with the apparition of a number of single detaching cells from the spheroid in a 5-FU dose- and cell line-dependent manner. We propose an innovative methodology for the chemosensitivity evaluation in 3D MCTS that recapitulates and regionalizes the 5-FU-induced changes within MCTS over time. These robust phenotypic read-outs could be easily scalable for high-throughput drug screening that may include different types of cancer cells to take into account tumor heterogeneity and resistance to treatment.
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spelling pubmed-56877322017-11-30 In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil Virgone-Carlotta, Angélique Lemasson, Manon Mertani, Hichem C. Diaz, Jean-Jacques Monnier, Sylvain Dehoux, Thomas Delanoë-Ayari, Hélène Rivière, Charlotte Rieu, Jean-Paul PLoS One Research Article MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-up of MCTS with simple and robust readouts to evaluate drug efficacy is still missing. Here, we evaluate the chemotherapeutic drug 5-Fluorouracil (5-FU) response on the growth and integrity of MCTS two days after treatment of MCTS and for three colorectal carcinoma cell lines with different cohesive properties (HT29, HCT116 and SW480). We found different sensitivity to 5-FU for the three CRC cell lines, ranging from high (SW480), intermediate (HCT116) and low (HT29) and the same hierarchy of CRC cell lines sensitivity is conserved in 2D. We also evidence that 5-FU has a strong impact on spheroid cohesion, with the apparition of a number of single detaching cells from the spheroid in a 5-FU dose- and cell line-dependent manner. We propose an innovative methodology for the chemosensitivity evaluation in 3D MCTS that recapitulates and regionalizes the 5-FU-induced changes within MCTS over time. These robust phenotypic read-outs could be easily scalable for high-throughput drug screening that may include different types of cancer cells to take into account tumor heterogeneity and resistance to treatment. Public Library of Science 2017-11-15 /pmc/articles/PMC5687732/ /pubmed/29141026 http://dx.doi.org/10.1371/journal.pone.0188100 Text en © 2017 Virgone-Carlotta et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Virgone-Carlotta, Angélique
Lemasson, Manon
Mertani, Hichem C.
Diaz, Jean-Jacques
Monnier, Sylvain
Dehoux, Thomas
Delanoë-Ayari, Hélène
Rivière, Charlotte
Rieu, Jean-Paul
In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title_full In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title_fullStr In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title_full_unstemmed In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title_short In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil
title_sort in-depth phenotypic characterization of multicellular tumor spheroids: effects of 5-fluorouracil
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687732/
https://www.ncbi.nlm.nih.gov/pubmed/29141026
http://dx.doi.org/10.1371/journal.pone.0188100
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