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Mitotic arrest affects clustering of tumor cells

BACKGROUND: Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic...

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Autores principales: Bonnet, Julia, Rigal, Lise, Mondesert, Odile, Morin, Renaud, Corsaut, Gaëlle, Vigneau, Mathieu, Ducommun, Bernard, Lobjois, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847029/
https://www.ncbi.nlm.nih.gov/pubmed/33514388
http://dx.doi.org/10.1186/s13008-021-00070-z
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author Bonnet, Julia
Rigal, Lise
Mondesert, Odile
Morin, Renaud
Corsaut, Gaëlle
Vigneau, Mathieu
Ducommun, Bernard
Lobjois, Valérie
author_facet Bonnet, Julia
Rigal, Lise
Mondesert, Odile
Morin, Renaud
Corsaut, Gaëlle
Vigneau, Mathieu
Ducommun, Bernard
Lobjois, Valérie
author_sort Bonnet, Julia
collection PubMed
description BACKGROUND: Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. RESULTS: In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. CONCLUSIONS: Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.
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spelling pubmed-78470292021-02-01 Mitotic arrest affects clustering of tumor cells Bonnet, Julia Rigal, Lise Mondesert, Odile Morin, Renaud Corsaut, Gaëlle Vigneau, Mathieu Ducommun, Bernard Lobjois, Valérie Cell Div Research BACKGROUND: Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. RESULTS: In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. CONCLUSIONS: Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells. BioMed Central 2021-01-29 /pmc/articles/PMC7847029/ /pubmed/33514388 http://dx.doi.org/10.1186/s13008-021-00070-z Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bonnet, Julia
Rigal, Lise
Mondesert, Odile
Morin, Renaud
Corsaut, Gaëlle
Vigneau, Mathieu
Ducommun, Bernard
Lobjois, Valérie
Mitotic arrest affects clustering of tumor cells
title Mitotic arrest affects clustering of tumor cells
title_full Mitotic arrest affects clustering of tumor cells
title_fullStr Mitotic arrest affects clustering of tumor cells
title_full_unstemmed Mitotic arrest affects clustering of tumor cells
title_short Mitotic arrest affects clustering of tumor cells
title_sort mitotic arrest affects clustering of tumor cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847029/
https://www.ncbi.nlm.nih.gov/pubmed/33514388
http://dx.doi.org/10.1186/s13008-021-00070-z
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