TY - JOUR
T1 - Exploring Cell Migration Mechanisms in Cancer
T2 - From Wound Healing Assays to Cellular Automata Models
AU - Migliaccio, Giorgia
AU - Ferraro, Rosalia
AU - Wang, Zhihui
AU - Cristini, Vittorio
AU - Dogra, Prashant
AU - Caserta, Sergio
N1 - Funding Information:
This research has been supported in part by the Cockrell Foundation (P.D.) and in part by the National Institutes of Health (NIH) Grants 1R01CA253865 (Z.W., V.C.), 1U01CA196403 (Z.W., V.C.), 1U01CA213759 (Z.W., V.C.), 1R01CA226537 (Z.W., V.C.), and 1R01CA222007 (Z.W., V.C.). The funders had no role in the study’s design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/11/3
Y1 - 2023/11/3
N2 - PURPOSE: Cell migration is a critical driver of metastatic tumor spread, contributing significantly to cancer-related mortality. Yet, our understanding of the underlying mechanisms remains incomplete.METHODS: In this study, a wound healing assay was employed to investigate cancer cell migratory behavior, with the aim of utilizing migration as a biomarker for invasiveness. To gain a comprehensive understanding of this complex system, we developed a computational model based on cellular automata (CA) and rigorously calibrated and validated it using in vitro data, including both tumoral and non-tumoral cell lines. Harnessing this CA-based framework, extensive numerical experiments were conducted and supported by local and global sensitivity analyses in order to identify the key biological parameters governing this process.RESULTS: Our analyses led to the formulation of a power law equation derived from just a few input parameters that accurately describes the governing mechanism of wound healing. This groundbreaking research provides a powerful tool for the pharmaceutical industry. In fact, this approach proves invaluable for the discovery of novel compounds aimed at disrupting cell migration, assessing the efficacy of prospective drugs designed to impede cancer invasion, and evaluating the immune system's responses.
AB - PURPOSE: Cell migration is a critical driver of metastatic tumor spread, contributing significantly to cancer-related mortality. Yet, our understanding of the underlying mechanisms remains incomplete.METHODS: In this study, a wound healing assay was employed to investigate cancer cell migratory behavior, with the aim of utilizing migration as a biomarker for invasiveness. To gain a comprehensive understanding of this complex system, we developed a computational model based on cellular automata (CA) and rigorously calibrated and validated it using in vitro data, including both tumoral and non-tumoral cell lines. Harnessing this CA-based framework, extensive numerical experiments were conducted and supported by local and global sensitivity analyses in order to identify the key biological parameters governing this process.RESULTS: Our analyses led to the formulation of a power law equation derived from just a few input parameters that accurately describes the governing mechanism of wound healing. This groundbreaking research provides a powerful tool for the pharmaceutical industry. In fact, this approach proves invaluable for the discovery of novel compounds aimed at disrupting cell migration, assessing the efficacy of prospective drugs designed to impede cancer invasion, and evaluating the immune system's responses.
KW - cancer invasion
KW - cell migration
KW - cellular automata model
KW - digital twin
KW - wound healing
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U2 - 10.3390/cancers15215284
DO - 10.3390/cancers15215284
M3 - Article
C2 - 37958456
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 21
M1 - 5284
ER -