Multiphase Mechanics of Tumor Encapsulation & Multilobulation

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Jackson0114473 The investigator uses mechanical models to investigate themechanisms involved in tumor encapsulation, multiple lobeformation, and transcapsular spread. Mass and momentum balanceequations are written for the normal cells, neoplastic cells, theextracellular matrix (ECM) on which they are anchored, and theinterstitial fluid in which they are bathed. This system isclosed by suitable constitutive relations for the mass supply,the partial stress tensor, and the momentum supply of eachconstituent. The former is defined on the basis ofphenomenological observations of tumor cell growth and the latteris based on the mechanical properties of each phase. The modelequations, consisting of a set nonlinear conservation andevolution equations, are analyzed using asymptotic analysis,bifurcation analysis, and perturbation theory in order toquantify the relative importance of chemical processes (such asECM production and degradation) and mechanical properties of thetissue (such as ECM density and stiffness) in influencing capsuleformation. A further objective is to characterize thebifurcation that leads to multiple lobe formation. Throughanalysis and simulation of the model, the investigator aims todiscover which factors (mechanical and chemical) determinesuccessful capsule formation and to quantify their influence. The mechanisms by which a tumor becomes encapsulated as acontinuum of cells or as several lobes of different sizes,separated by connective tissue, is an interesting, important, andunsolved phenomenon in tumor biology. In fact, the presence (orabsence) of a dense capsule surrounding a neoplastic mass is amajor determinant of prognosis and the ultimate survival of thehost. Despite the importance of capsule formation, little isknown about the process by which capsules arise. Theincestigator develops a mathematical modeling framework thatdescribes tumor growth, encapsulation, multiple lobe formation,and transcapsular spread based on the physical forces andcellular interactions involved. The specific aims are to usemechanical models to assist in understanding i) the role tumorcell, normal cell, and extracellular matrix (ECM) interactions incapsule formation, ii) the effects of tumor induced ECMproduction and degradation on the formation of tumor capsules,iii) the role of tissue properties such as ECM density andstiffness in slowing or impeding the process of tumorencapsulation, and iv) the bifurcation that allows a simpleencapsulated continuum of cells to make the transition to amulti-nodular form. There are implications for clinical diagnosisas well as for prognosis.