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Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D
BACKGROUND: MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598667/ https://www.ncbi.nlm.nih.gov/pubmed/23394599 http://dx.doi.org/10.1186/1471-2407-13-73 |
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author | Laurent, Jennifer Frongia, Céline Cazales, Martine Mondesert, Odile Ducommun, Bernard Lobjois, Valérie |
author_facet | Laurent, Jennifer Frongia, Céline Cazales, Martine Mondesert, Odile Ducommun, Bernard Lobjois, Valérie |
author_sort | Laurent, Jennifer |
collection | PubMed |
description | BACKGROUND: MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D. METHODS: Cell cycle and proliferation parameters were investigated in Capan-2 spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters. RESULTS: We describe in details the changes in proliferation and cell cycle parameters during spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage. CONCLUSION: Our data present the power and the limitation of spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models. |
format | Online Article Text |
id | pubmed-3598667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35986672013-03-16 Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D Laurent, Jennifer Frongia, Céline Cazales, Martine Mondesert, Odile Ducommun, Bernard Lobjois, Valérie BMC Cancer Research Article BACKGROUND: MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D. METHODS: Cell cycle and proliferation parameters were investigated in Capan-2 spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters. RESULTS: We describe in details the changes in proliferation and cell cycle parameters during spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage. CONCLUSION: Our data present the power and the limitation of spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models. BioMed Central 2013-02-08 /pmc/articles/PMC3598667/ /pubmed/23394599 http://dx.doi.org/10.1186/1471-2407-13-73 Text en Copyright ©2013 Laurent et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Laurent, Jennifer Frongia, Céline Cazales, Martine Mondesert, Odile Ducommun, Bernard Lobjois, Valérie Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title | Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title_full | Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title_fullStr | Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title_full_unstemmed | Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title_short | Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D |
title_sort | multicellular tumor spheroid models to explore cell cycle checkpoints in 3d |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598667/ https://www.ncbi.nlm.nih.gov/pubmed/23394599 http://dx.doi.org/10.1186/1471-2407-13-73 |
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