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Modeling and Imaging 3-Dimensional Collective Cell Invasion
Published on: December 7, 2011
An integrated computational/experimental model of tumor invasion
Hermann B Frieboes1, Xiaoming Zheng, Chung-Ho Sun
1Department of Biomedical Engineering, University of California-Irvine, Irvine, CA 92697-2715, USA.
Cancer Research
|February 3, 2006
Summary
Tumor growth and invasion depend on cell proliferation and mechanical forces. Mathematical modeling and in vitro studies show that spatial nutrient gradients can destabilize tumors, promoting invasion and potentially worsening outcomes with current therapies.
Area of Science:
- * Oncology and Mathematical Biology: Investigating the interplay between cellular dynamics, microenvironment, and tumor morphology.
- * Glioblastoma Research: Utilizing human and rat glioblastoma models to understand invasive growth patterns.
Background:
- * Tumor growth and invasiveness are complex processes influenced by intracellular/extracellular dynamics, cell characteristics, and microenvironmental factors (nutrients, oxygen, growth factors).
- * Previous mathematical models suggested tumor morphology arises from a balance between proliferation-driven instability and stabilizing mechanical forces.
Purpose of the Study:
- * To test the hypothesis that tumor morphology is determined by the competition between heterogeneous cell proliferation and stabilizing mechanical forces.
- * To investigate the role of spatial diffusion gradients in driving tumor shape instability and invasive morphologies.
- * To analyze glioma spheroid stability using a reaction-diffusion mathematical model.
Main Methods:
- * Development of a reaction-diffusion mathematical model incorporating tumor cell cycle and biology variables.
- * Acquisition of variable-based statistics from in vitro human and rat glioblastoma cultures.
- * Linear stability analysis of the mathematical model and computer simulations.
Main Results:
- * Mathematical model predicted marginally stable glioma spheroid morphology.
- * In vitro experiments showed unbounded growth and invasion, characterized by recursive subspheroid development and separation.
- * Computer simulations closely replicated observed in vitro tumor morphologies and cell arrangements.
Conclusions:
- * Tumor morphogenesis in vivo may result from marginally stable conditions driven by spatial microenvironmental gradients.
- * Reducing spatial gradients in nutrients, oxygen, and growth factors could improve treatment outcomes.
- * Current therapies, including antiangiogenic treatments, may inadvertently increase spatial heterogeneity and promote invasive instability.
