TY - JOUR
T1 - Hybrid Cellular Automata Modeling Reveals the Effects of Glucose Gradients on Tumour Spheroid Growth
AU - Messina, Luca
AU - Ferraro, Rosalia
AU - Peláez, Maria J.
AU - Wang, Zhihui
AU - Cristini, Vittorio
AU - Dogra, Prashant
AU - Caserta, Sergio
N1 - Funding Information:
This work was partially supported by funding from the Cockrell Foundation (PD). This study was conducted under the umbrella of the International Academic Affiliation Agreement between Houston Methodist Academic Institute (Houston, TX, USA) and the University of Naples Federico II (Napoli, Italy).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/11/30
Y1 - 2023/11/30
N2 - Purpose: 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. Methods: 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. Results: 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.
AB - Purpose: 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. Methods: 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. Results: 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.
KW - agent-based modeling
KW - cancer
KW - hybrid cellular automata
KW - tumor spheroid
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U2 - 10.3390/cancers15235660
DO - 10.3390/cancers15235660
M3 - Article
C2 - 38067364
AN - SCOPUS:85179322672
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 23
M1 - 5660
ER -