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Unsuccessful mitosis in multicellular tumour spheroids
Annie Molla1, Morgane Couvet1, Jean-Luc Coll1
1Institute for Advance Biosciences, Centre de recherche UGA, INSERM U1209, CNRS UMR 5309, 38700 La Tronche, France.
Oncotarget
|April 22, 2017
Summary
Multicellular spheroids, used in oncology, show increased binucleated cells due to failed cytokinesis during mitosis. These 3D tumor models are sensitive to mitotic drugs, aiding cancer research.
Area of Science:
- Oncology
- Cell Biology
- Biotechnology
Background:
- Multicellular spheroids mimic tumor 3D organization and microenvironment.
- Increased binucleated cells are observed in some human tumors.
Purpose of the Study:
- To investigate the cell division process in multicellular spheroids.
- To determine the relevance of spheroids as cancer models for drug testing.
Main Methods:
- Utilized three cell types (TSA/pc, Hek293, HeLa) in spheroid culture.
- Observed mitosis using mitotic markers and time-lapse experiments.
- Assessed spheroid sensitivity to mitotic drugs like paclitaxel and aurora kinase inhibitors.
Main Results:
- Spheroids exhibit augmented binucleated cells, similar to human tumors.
- Mitosis proceeds with correct chromosome alignment and spindle checkpoint satisfaction.
- Cytokinesis fails, leading to binucleated cells and loss of division orientation regulation.
- Spheroid expansion remains sensitive to mitotic drugs.
Conclusions:
- Multicellular spheroids accurately model tumor cell behavior, including binucleation and orientation defects.
- Spheroids are a relevant in vitro model for evaluating the efficacy of anti-cancer drugs targeting mitosis.