Abstract 560: Mechanical stress activates a mitotic checkpoint in multicellular tumor spheroids.

Abstract

Abstract Expanding solid tumors are subjected to mechanical stress that impact on their growth rate and development. However little is known on the mechanisms by which mechanical cues are acting on tumor cell biology. To address that issue, we used MultiCellular Tumor Spheroid (MCTS), a 3D model recapitulating the microenvironment, the proliferative gradient and cell-cell interactions found in a tumor. To test the impact of mechanical stress on tumor cell proliferation, we first designed, produced and used dedicated polymer microdevices in which MCTS engineered to express fluorescent biomarkers were confined to apply mechanical constraints. We observe that under constraints, MCTS display a high proportion of mitotic cells in low proliferative regions of confined spheroids. We show that these cells are being arrested in mitosis for at least 24 hours (EdU incorporation neg.) and that mitotic arrest is not caused by impairment of rounding. We next used live SPIM (Selective Plane Illumination Microscopy) 3D imaging to monitor mitosis progression in isotropically constrained MCTS. We show that constraint impairs bipolar spindle assembly and delays progression toward metaphase-anaphase transition. Our data indicate that in a multicellular structure mechanical constraints are responsible for a defect in cell cycle progression associated with a mitotic arrest. Citation Format: Annaïck Desmaison, Katia Grenier, Celine Frongia, Corinne Lorenzo, Bernard Ducommun, Valerie Lobjois. Mechanical stress activates a mitotic checkpoint in multicellular tumor spheroids. [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 560. doi:10.1158/1538-7445.AM2013-560