A model for membrane degradation using a gelatin invadopodia assay

Giorgia Ciavolella, Nathalie Ferrand, Michèle Sabbah, Benoît Perthame, Roberto Natalini
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Abstract

One of the most crucial and lethal characteristics of solid tumors is represented by the increased ability of cancer cells to migrate and invade other organs during the so-called metastatic spread. This is allowed thanks to the production of matrix metalloproteinases (MMPs), enzymes capable of degrading a type of collagen abundant in the basal membrane separating the epithelial tissue from the connective one. In this work, we employ a synergistic experimental and mathematical modelling approach to explore the invasion process of tumor cells. A athematical model composed of reaction-diffusion equations describing the evolution of the tumor cells density on a gelatin substrate, MMPs enzymes concentration and the degradation of the gelatin is proposed. This is completed with a calibration strategy. We perform a sensitivity analysis and explore a parameter estimation technique both on synthetic and experimental data in order to find the optimal parameters that describe the in vitro experiments. A comparison between numerical and experimental solutions ends the work.
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使用明胶内陷试验的膜降解模型
实体瘤最关键和最致命的特征之一是癌细胞在所谓的转移扩散过程中迁移和侵入其他器官的能力增强。这要归功于基质金属蛋白酶(MMPs)的产生,这种酶能够降解分隔上皮组织和结缔组织的基底膜上丰富的胶原蛋白。在这项工作中,我们采用非协同实验和数学建模方法来探索肿瘤细胞的入侵过程。我们提出了一个由反应-扩散方程组成的数学模型,描述了明胶基质上肿瘤细胞密度、MMPs 酶浓度和明胶降解的演变过程。最后提出了校准策略。我们对合成数据和实验数据进行了敏感性分析,并探索了参数估计技术,以找到描述体外实验的最佳参数。最后,对数值解和实验解进行了比较。
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