Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Abstract

Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, 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's fluidity and stiffness. 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 on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.

Different contractility modes control cell escape from multicellular spheroids and tumor explants

“…With that, a subpopulation with a high stress fiber-based contractility could escape into the ECM, while another subpopulation can generate a collective actin structure and a smooth boundary. 46,47 A similar behavior is seen for a second piece of the MMMT explant on the same collagen substrate [see left in Fig. 3(d) ].…”

“…To achieve a coherent understanding, we also assess the boundary texture of the tumor pieces. 46 The IDC explant does not show any smoothing of the boundaries as would be caused by active tissue surface tension and bulk contraction. Instead, the boundary keeps being rough and numerous cell motion throughout the whole sample (see supplementary material Video S5) can be seen, suggesting a low tissue surface tension.…”

Beyond stiffness: deciphering the role of viscoelasticity in cancer evolution and treatment response

“…Moreover, a recent meta-analysis of in vivo MRE studies indicated that while there was an increase in stiffness for most of the tumors considered (including malignant and benign liver, brain, pancreas, prostate, and colorectal cancer), this was accompanied by a significant increase in fluidity. The only exception was brain glioblastoma, which experienced a decrease in both stiffness and fluidity during cancer progression [103]. As explained in sections 2.2 and 2.3, an increase in tissue fluidity is linked to an increased invasion potential (figure 1(C)).…”

Mechanobiology in oncology: basic concepts and clinical prospects

“…The prognostic potential enhances when examining other rheological properties of the tumor microenvironment through the application of in vivo multifrequency magnetic resonance elastography (MRE). Employing this technique, Sauer et al (2023) outlined a roadmap for prognosis of a tumor's aggressiveness and metastatic potential based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor (Figure 2C). They showed that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales."…”