Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Abstract

AbstractCancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increasedstiffnesshas been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissuefluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue'sfluidityandstiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based onstiffness, fluidity,spatial heterogeneity, andtextureof thetumor fronta roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.