MultiCellular Tumor Spheroid (MCTS) mimic the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. We report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization, the dynamics of cell cycle checkpoints and the effects of anticancer drugs in 3D. Spheroids expressing fluorescent reporters were engineered and used to explore cell cycle distribution and regionalization during growth. In these models we monitored cell cycle arrest in response to checkpoint activation after growth factor starvation, DNA injury or treatment with chemotherapeutic agents. The kinetics and regionalized aspects of the response were investigated both on fixed sections and on live spheroids using light sheet microscopy. All together, our data demonstrate the power of the combination of spheroids made of genetically modified cells expressing cell cycle reporters with both classical antibody-based detection and the use of innovative 3D imaging strategy. This study paves the way for the investigation of the molecular aspects of checkpoint response in 3D models and the dynamic studies of the 3D response to novel antiproliferative agents.

Citation Format: Bernard Ducommun, Valérie Lobjois, Jennifer Laurent, Céline Frongia, Odile Mondesert, Martine Cazales. Multicellular tumor spheroid models to evaluate drugs targeting cell cycle checkpoints in 3D. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4404. doi:10.1158/1538-7445.AM2013-4404