Poster

Changes in tissue stiffness and fluidity predict tumor aggressiveness in vivo

Frank Sauer¹, Steffen Grosser¹, Mehrgan Shahryari², Alexander Hayn³, Jing Guo², Jürgen Braun⁴, Susanne Briest⁵, Benjamin Wolf⁵, Bahriye Aktas⁵, Lars-Christian Horn⁶, Ingolf Sack², Josef A. Käs¹

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Cancer progression is associated with a variety of effects that affect a tissue’s mechanical state. While increased tumor stiffness alone cannot predict clinical outcomes, we hypothesize that cancer progression is also accompanied by tissue fluidization. State-of-the-art in vivo multifrequency Magnetic Resonance Elastography (MRE) can differentiate individual tumors from their surrounding tissues by their rheological signature. We found universal trends in an analysis of several clinical MRE in vivo studies. Backed by tabletop MRE experiments on stroma mimicking collagen gels and microscopic analysis of live cells inside human tumor explants, we present an overview of possible underlying mechanism, including cellular unjamming, microenvironment composition/remodeling and emergent effects, which may critically determine tumor progression and their potential influence bulk mechanics. Based on that we performed a gedankenexperiment about how a tumor can grow and eventually metastasize in its environment from a physics perspective and deduced corresponding macroscopic mechanical properties. Identified parameters of relevance are stiffness, fluidity, spatial fluidity heterogeneity, and tumor border texture. Finally, we present a roadmap for using MRE-acquired information to predict a tumor’s aggressiveness and metastatic potential in individual patients.