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Analysis of Energy-Driven Leader-Follower Hierarchy During Collective Cancer Cell Invasion

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Cell Migration in Three Dimensions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2608))

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Abstract

Many solid tumors can invade the surrounding three-dimensional (3D) tissue in a collective manner, and increasing evidence suggests that collective migration makes cancer cell clusters more invasive and metastatic than individual cells. A cohesive cohort of cancer cells can have many advantages over individual cells, including more efficient bioenergetics that have been recently identified. Minimization of bioenergetic costs during collective cell migration drives leader-follower dynamics and contributes to enhanced cancer invasion. Hence, it is critical to understand the migratory and bioenergetic dynamics of cancer collective invasion. While analysis of structures and dynamics in a 3D space has been a challenging task, here we describe a widely applicable method to analyze the energy-driven leader-follower hierarchy during cancer collective invasion. An in vitro tumor spheroid model is employed to reproduce the in vivo collective behaviors of cancer cells while allowing high spatiotemporal resolution imaging, where the leader-follower dynamics can be analyzed by tracking nuclear positions. As glucose is one of the main energy sources that fuel cancer cell migration, the quantification of glucose uptake along the invading strands provides an estimate of the energy demand associated with collective invasion. Finally, we describe a method to quantify the dynamics of intracellular energy level using the PercevalHR ATP:ADP ratio biosensor.

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Acknowledgments

This work was supported by funding from the National Institutes of Health (HL127499 and GM13117) and the W.M. Keck Foundation to C.A.R.-K.

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Correspondence to Cynthia A. Reinhart-King .

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Zhang, J., Reinhart-King, C.A. (2023). Analysis of Energy-Driven Leader-Follower Hierarchy During Collective Cancer Cell Invasion. In: Margadant, C. (eds) Cell Migration in Three Dimensions. Methods in Molecular Biology, vol 2608. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2887-4_15

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  • DOI: https://doi.org/10.1007/978-1-0716-2887-4_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2886-7

  • Online ISBN: 978-1-0716-2887-4

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