Spatiotemporal dynamics of the biological interface between cancer and the microenvironment: A fractal anomalous diffusion model with microenvironment plasticity

Feng-Chou Tsai, Mei Chuan Wang, Jeng Fan Lo, Chih Ming Chou, Yi Lu Lin

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: The invasion-metastasis cascade of cancer involves a process of parallel progression. A biological interface (module) in which cells is linked with ECM (extracellular matrix) by CAMs (cell adhesion molecules) has been proposed as a tool for tracing cancer spatiotemporal dynamics. Methods: A mathematical model was established to simulate cancer cell migration. Human uterine leiomyoma specimens, in vitro cell migration assay, quantitative realtime PCR, western blotting, dynamic viscosity, and an in vivo C57BL6 mouse model were used to verify the predictive findings of our model. Results: The return to origin probability (RTOP) and its related CAM expression ratio in tumors, so-called "tumor self-seeding", gradually decreased with increased tumor size, and approached the 3D Pólya random walk constant (0.340537) in a periodic structure. The biphasic pattern of cancer cell migration revealed that cancer cells initially grew together and subsequently began spreading. A higher viscosity of fillers applied to the cancer surface was associated with a significantly greater inhibitory effect on cancer migration, in accordance with the Stokes-Einstein equation. Conclusion: The positional probability and cell-CAM-ECM interface (module) in the fractal framework helped us decipher cancer spatiotemporal dynamics; in addition we modeled the methods of cancer control by manipulating the microenvironment plasticity or inhibiting the CAM expression to the Pólya random walk, Pólya constant.

Original languageEnglish
Article number36
JournalTheoretical Biology and Medical Modelling
Volume9
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • Anomalous diffusion
  • Cancer
  • Integrins
  • Metastasis
  • Pálya constant
  • Probability
  • Random walk
  • Tumor self-seeding

ASJC Scopus subject areas

  • Health Informatics
  • Modelling and Simulation
  • Medicine(all)

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