Multiphase Mechanics of Tumor Encapsulation & Multilobulation

肿瘤包膜的多相力学

• 批准号: 0114473
• 负责人: Trachette Jackson
• 金额: $ 10.1万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0114473&HistoricalAwards=false
• 关键词: Multiphase; Mechanics; Tumor; Encapsulation; &amp

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.

杰克逊0114473 研究者使用力学模型来研究肿瘤包裹、多叶形成和跨囊扩散的机制。 对于正常细胞、肿瘤细胞、它们所锚定的细胞外基质（ECM）以及它们所沐浴的间质液，写出了质量和动量平衡方程。 这个系统是封闭的适当的本构关系的质量供应，偏应力张量，和动量供应的每个组成部分。 前者是基于对肿瘤细胞生长的现象学观察而定义的，后者是基于每个相的力学性质。 模型方程，由一组非线性守恒和演化方程，分析使用渐近分析，分叉分析，和扰动理论，以量化的相对重要性的化学过程（如ECM的生产和降解）和机械性能的组织（如ECM密度和刚度）在影响囊形成。 另一个目的是描述导致多叶形成的分叉。 通过对模型的分析和模拟，研究者旨在发现哪些因素（机械和化学）决定了成功的胶囊形成并量化它们的影响。 肿瘤被结缔组织包裹成一个连续的细胞或几个大小不同的小叶，这是肿瘤生物学中一个有趣的、重要的和未解决的现象。 事实上，肿瘤周围致密包膜的存在与否是预后和宿主最终存活的一个主要决定因素。 尽管胶囊形成的重要性，很少有人知道胶囊产生的过程。 研究者建立了一个数学模型框架，根据物理力和细胞相互作用描述肿瘤生长、包膜、多叶形成和跨囊扩散。 具体目的是使用力学模型来帮助理解i）肿瘤细胞、正常细胞和细胞外基质（ECM）相互作用对肿瘤形成的作用，ii）肿瘤诱导的ECM产生和降解对肿瘤包膜形成的作用，iii）组织特性如ECM密度和刚度在减缓或阻碍肿瘤包膜形成过程中的作用，以及iv）分叉，其允许细胞的简单包裹连续体转变为多结节形式。 这对临床诊断和预后都有意义。