Exploring Cell Migration Mechanisms in Cancer: From Wound Healing Assays to Cellular Automata Models
by
, and
Giorgia Migliaccio
1,†, 
Rosalia Ferraro
1,2,†
,
Zhihui Wang
3,4,5,6,
Vittorio Cristini
3,4,5,7,
Prashant Dogra
3,6 and
Sergio Caserta
1,2,*
1
Dipartimento di Ingegneria Chimica, dei Materiali e Della Produzione Industriale, Università Degli Studi di Napoli Federico II, 80125 Naples, Italy
2
CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 80145 Naples, Italy
3
Mathematics in Medicine Program, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA
4
Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA
5
Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
6
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA
7
Physiology, Biophysics, and Systems Biology Program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2023, 15(21), 5284; https://doi.org/10.3390/cancers15215284
Submission received: 12 October 2023
/
Revised: 24 October 2023
/
Accepted: 1 November 2023
/
Published: 3 November 2023
(This article belongs to the Special Issue Experimental and Modeling Efforts to Target Metabolism in Cancer)
Simple Summary
Cell migration is a key factor in the spread of metastatic tumors and a major contributor to cancer-related mortality. However, our comprehension of the underlying mechanisms remains incomplete. In this study, we utilized a wound healing assay to explore the migration and invasion of cancer cells in the context of metastasis. We developed a computational model using cellular automata, rigorously calibrated and validated with in vitro data from both tumor and non-tumor cell lines, offering a potent resource. This novel approach is of immense value to the pharmaceutical sector for discovering compounds that can impede cell migration, evaluating the efficacy of potential drugs to hinder cancer invasion, and assessing immune system responses. It stands as a breakthrough in the quest for more effective cancer therapies.
Abstract
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.
