Exploring Cell Migration Mechanisms in Cancer: From Wound Healing Assays to Cellular Automata Models

Author:

Migliaccio Giorgia1,Ferraro Rosalia12ORCID,Wang Zhihui3456,Cristini Vittorio3457,Dogra Prashant36ORCID,Caserta Sergio12ORCID

Affiliation:

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

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.

Funder

Cockrell Foundation

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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