Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

作者：Yafei Wang, Erik Brodin, Kenichiro Nishii, Hermann B. Frieboes, Shannon M. Mumenthaler, Jessica L. Sparks, Paul Macklin · 发表于：Scientific Reports · 年份：2021 · DOI：10.1038/s41598-020-78780-7 · 被引用次数：36 · 研究领域：Cellular Mechanics and Interactions、Mathematical Biology Tumor Growth、3D Printing in Biomedical Research

Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing succe...