Multiphase Mechanics of Tumor Encapsulation & Multilobulation

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Jackson 0114473 The investigator uses mechanical models to investigate the mechanisms involved in tumor encapsulation, multiple lobe formation, and transcapsular spread. Mass and momentum balance equations are written for the normal cells, neoplastic cells, the extracellular matrix (ECM) on which they are anchored, and the interstitial fluid in which they are bathed. This system is closed by suitable constitutive relations for the mass supply, the partial stress tensor, and the momentum supply of each constituent. The former is defined on the basis of phenomenological observations of tumor cell growth and the latter is based on the mechanical properties of each phase. The model equations, consisting of a set nonlinear conservation and evolution equations, are analyzed using asymptotic analysis, bifurcation analysis, and perturbation theory in order to quantify the relative importance of chemical processes (such as ECM production and degradation) and mechanical properties of the tissue (such as ECM density and stiffness) in influencing capsule formation. A further objective is to characterize the bifurcation that leads to multiple lobe formation. Through analysis and simulation of the model, the investigator aims to discover which factors (mechanical and chemical) determine successful capsule formation and to quantify their influence. The mechanisms by which a tumor becomes encapsulated as a continuum of cells or as several lobes of different sizes, separated by connective tissue, is an interesting, important, and unsolved phenomenon in tumor biology. In fact, the presence (or absence) of a dense capsule surrounding a neoplastic mass is a major determinant of prognosis and the ultimate survival of the host. Despite the importance of capsule formation, little is known about the process by which capsules arise. The incestigator develops a mathematical modeling framework that describes tumor growth, encapsulation, multiple lobe formation, and transcapsular spread based on the physical forces and cellular interactions involved. The specific aims are to use mechanical models to assist in understanding i) the role tumor cell, normal cell, and extracellular matrix (ECM) interactions in capsule formation, ii) the effects of tumor induced ECM production and degradation on the formation of tumor capsules, iii) the role of tissue properties such as ECM density and stiffness in slowing or impeding the process of tumor encapsulation, and iv) the bifurcation that allows a simple encapsulated continuum of cells to make the transition to a multi-nodular form. There are implications for clinical diagnosis as well as for prognosis.