Messina Luca, Ferraro Rosalia, Peláez Maria J, Wang Zhihui, Cristini Vittorio, Dogra Prashant, Caserta Sergio
Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, 80125 Naples, Italy.
CEINGE-Biotecnologie Avanzate Franco Salvatore, Via G. Salvatore 436, 80131 Naples, Italy.
Cancers (Basel). 2023 Nov 30;15(23):5660. doi: 10.3390/cancers15235660.
In recent years, mathematical models have become instrumental in cancer research, offering insights into tumor growth dynamics, and guiding the development of pharmacological strategies. These models, encompassing diverse biological and physical processes, are increasingly used in clinical settings, showing remarkable predictive precision for individual patient outcomes and therapeutic responses.
Motivated by these advancements, our study introduces an innovative in silico model for simulating tumor growth and invasiveness. The automated hybrid cell emulates critical tumor cell characteristics, including rapid proliferation, heightened motility, reduced cell adhesion, and increased responsiveness to chemotactic signals. This model explores the potential evolution of 3D tumor spheroids by manipulating biological parameters and microenvironment factors, focusing on nutrient availability.
Our comprehensive global and local sensitivity analysis reveals that tumor growth primarily depends on cell duplication speed and cell-to-cell adhesion, rather than external chemical gradients. Conversely, tumor invasiveness is predominantly driven by chemotaxis. These insights illuminate tumor development mechanisms, providing vital guidance for effective strategies against tumor progression. Our proposed model is a valuable tool for advancing cancer biology research and exploring potential therapeutic interventions.
近年来,数学模型在癌症研究中发挥了重要作用,有助于深入了解肿瘤生长动态,并指导药理学策略的制定。这些模型涵盖了各种生物和物理过程,越来越多地应用于临床环境,对个体患者的预后和治疗反应显示出显著的预测精度。
受这些进展的启发,我们的研究引入了一种创新的计算机模拟模型,用于模拟肿瘤生长和侵袭性。自动混合细胞模拟关键的肿瘤细胞特征,包括快速增殖、高运动性、降低的细胞粘附性以及对趋化信号的增强反应性。该模型通过操纵生物学参数和微环境因素,重点关注营养物质的可用性,探索三维肿瘤球体的潜在演变。
我们全面的全局和局部敏感性分析表明,肿瘤生长主要取决于细胞复制速度和细胞间粘附,而不是外部化学梯度。相反,肿瘤侵袭主要由趋化作用驱动。这些见解阐明了肿瘤发展机制,为对抗肿瘤进展的有效策略提供了重要指导。我们提出的模型是推进癌症生物学研究和探索潜在治疗干预措施的宝贵工具。