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.
目的：细胞迁移是肿瘤转移扩散的关键驱动因素，对癌症相关死亡率具有重要影响。然而，我们对其潜在机制的理解仍不完整。方法：本研究采用伤口愈合实验探究癌细胞迁移行为，旨在将迁移能力作为侵袭性的生物标志物。为全面理解这一复杂系统，我们基于元胞自动机（CA）开发了计算模型，并利用体外数据（包括肿瘤性和非肿瘤性细胞系）对其进行了严格校准与验证。借助这一CA框架，我们开展了大量数值实验，并通过局部与全局敏感性分析加以支持，以识别调控该过程的关键生物学参数。结果：我们的分析推导出一个仅需少量输入参数即可准确描述伤口愈合调控机制的幂律方程。这项突破性研究为制药行业提供了有力工具。实际上，该方法在发现靶向细胞迁移的新型化合物、评估旨在抑制癌症侵袭的候选药物疗效，以及分析免疫系统反应方面具有重要价值。
Exploring Cell Migration Mechanisms in Cancer: From Wound Healing Assays to Cellular Automata Models
肿瘤(癌症)患者之家