Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D

BMC Cancer

Jennifer Laurent¹  Céline Frongia¹  Martine Cazales¹  Odile Mondesert¹  Bernard Ducommun²  Valérie Lobjois³ 

[1] CNRS; ITAV-USR3505, F-31106, Toulouse, France

[2] CHU de Toulouse, F-31059, Toulouse, France

[3] ITAV - USR3505, Centre Pierre Potier, 1 place Pierre Potier, 50624, 31106, Toulouse Cedex 1, BP, France

关键词: Fucci reporters;    Checkpoint;    Cell cycle;    3D;    Spheroid;   

Others  :  1079917
DOI  :  10.1186/1471-2407-13-73

 received in 2012-08-02, accepted in 2013-02-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Laurent et al; licensee BioMed Central Ltd.

【 图 表 】

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