Abstract 1100: Dynamic multicellular mechanics controlling protrusion in 3D.

Abstract

Abstract Despite much effort, the transition from benign to malignant breast cancer remains poorly understood, resulting in overtreatment of women with in situ lesions. A growing appreciation for the role of cell mechanics in driving cell behavior has prompted interest in how mechanical interactions might control tumor growth and progression. How these parameters impact the transition from benign to malignant breast cancer remains unclear. Mechanical interactions among cells via adherens junctions, and between cells and the ECM via focal adhesions, can each exert dominant effects on cell behavior. Cell motility and invasion require force interactions by harnessing cytoskeletal dynamics, which permit shape changes and generate and transmit forces. Tension maintained across the actin cortex mechanically restricts protrusions, and may be transmitted across multiple cells via adherens junctions. Thus epithelial cells form mechanically integrated tissues that may be responsive to changes in cortical tension over great distances. However, the regulatory role of cortical tension in restricting cells from protruding is unclear. Overall, we lack detailed morphologic and mechanical models of cell protrusion and invasion out of 3D collectives. Using MDCK cell exposure to HGF as a model for rupture of epithelial integrity and protrusion, we have demonstrated the morphologic parameters that permit protrusion of a cell from its surrounding epithelium. Combined with work from our lab on force interactions between cells via adherens junctions, as well as mechanical interactions between a cell and its substrate, we may extrapolate detailed force interactions that underlie the observed cell shape and motility parameters that permit protrusion. Citation Format: Timothy Fessenden, Margaret L. Gardel. Dynamic multicellular mechanics controlling protrusion 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 1100. doi:10.1158/1538-7445.AM2013-1100