PREDICTING THE ROLE OF MICROSTRUCTURAL AND BIOMECHANICAL CUES IN TUMOR GROWTH AND SPREADING

Abstract

A multitude of mathematical and computational approaches have been proposed for predicting tumor growth. Yet, most models treat malignant masses as fluids neglecting microstructural and biomechanical features of the tumor extracellular matrix (ECM). Here, a continuum porous media model is developed within the thermodynamically constrained averaging theory (TCAT) framework for elucidating the role of these mechanical cues in regulating tumor growth and spreading. The model comprises three fluid phases – tumor cells, host cells, and interstitial fluid – and a solid phase – the ECM – considered as an elasto-visco-plastic medium. After validating the computational model against a multicellular tumor spheroid of glioblastoma multiforme, the effect on tumor development of ECM stiffness, adhesion with tumor cells and porosity is investigated. It is shown that stiffer matrices and higher cell-matrix adhesion limit tumor growth and spreading towards the surrounding tissue. A decrease in ECM Young's modulus E from 600 to 200 Pa induces a 60% increase in tumor mass within 8 days of observation. Similarly, a decrease of the adhesion parameter μ from 40 to 5 is responsible for an increase in tumor mass of 100%. On the other hand, higher matrix porosities favor the growth of the malignant mass and the dissemination of tumor cells. A modest increase in the porosity parameter ε from 0.7 to 0.9 is associated with a 300% increase in tumor mass. This model could be used for predicting the response of malignant masses to novel therapeutic agents affecting directly the tumor microenvironment and its micromechanical cues.

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