Mitotic arrest affects clustering of tumor cells
Abstract 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 chemother...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Cell Division |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13008-021-00070-z |
| _version_ | 1818732062062936064 |
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| author | Julia Bonnet Lise Rigal Odile Mondesert Renaud Morin Gaëlle Corsaut Mathieu Vigneau Bernard Ducommun Valérie Lobjois |
| author_facet | Julia Bonnet Lise Rigal Odile Mondesert Renaud Morin Gaëlle Corsaut Mathieu Vigneau Bernard Ducommun Valérie Lobjois |
| author_sort | Julia Bonnet |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T23:27:35Z |
| format | Article |
| id | doaj.art-61bd59c5a4124a488c98c8c42a1caf13 |
| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-12-17T23:27:35Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj.art-61bd59c5a4124a488c98c8c42a1caf132022-12-21T21:28:45ZengBMCCell Division1747-10282021-01-0116111310.1186/s13008-021-00070-zMitotic arrest affects clustering of tumor cellsJulia Bonnet0Lise Rigal1Odile Mondesert2Renaud Morin3Gaëlle Corsaut4Mathieu Vigneau5Bernard Ducommun6Valérie Lobjois7Université de Toulouse, ITAV, CNRSUniversité de Toulouse, ITAV, CNRSUniversité de Toulouse, ITAV, CNRSIMACTIV-3D SASUniversité de Toulouse, ITAV, CNRSUniversité de Toulouse, ITAV, CNRSUniversité de Toulouse, ITAV, CNRSUniversité de Toulouse, ITAV, CNRSAbstract 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.https://doi.org/10.1186/s13008-021-00070-zCancer cell clusteringMitosisMicrotubule-targeting agentsAnchorage-independent aggregationQuantitative live imaging |
| spellingShingle | Julia Bonnet Lise Rigal Odile Mondesert Renaud Morin Gaëlle Corsaut Mathieu Vigneau Bernard Ducommun Valérie Lobjois Mitotic arrest affects clustering of tumor cells Cell Division Cancer cell clustering Mitosis Microtubule-targeting agents Anchorage-independent aggregation Quantitative live imaging |
| 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 | Cancer cell clustering Mitosis Microtubule-targeting agents Anchorage-independent aggregation Quantitative live imaging |
| url | https://doi.org/10.1186/s13008-021-00070-z |
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