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Updated: Jul 19, 2026
06:36
A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion
Published on: April 24, 2015
Metabolic changes during carcinogenesis: potential impact on invasiveness.
Kieran Smallbone1, Robert A Gatenby, Robert J Gillies
1Centre for Mathematical Biology, Mathematical Institute, 24-29 St Giles', Oxford, OX1 3LB, UK. kieran.smallbone@manchester.ac.uk
Journal of Theoretical Biology
|October 24, 2006
Summary
Cancer cells adapt to their environment through three evolutionary phases, driven by changes in oxygen, glucose, and pH. Targeting this hypoxia-glycolysis-acidosis cycle may prevent cancer progression.
Area of Science:
- Oncology
- Computational Biology
- Cell Biology
Background:
- Carcinogenesis involves complex cell-microenvironment interactions.
- Understanding somatic evolution in premalignant lesions is critical for cancer prevention.
Purpose of the Study:
- To investigate cell-microenvironmental interactions driving cancer somatic evolution.
- To model the impact of substrate-limited environments on cancer cell adaptation.
Main Methods:
- Development of a hybrid cellular automation model.
- Simulation of cell proliferation, metabolism, and environmental changes (oxygen, glucose, pH).
Main Results:
- Identified three phases of cancer cell evolution: hypoxia-limited, glycolysis-dominated, and acid-resistant.
- Demonstrated that metabolic adaptation to low oxygen and high acidity provides a proliferative advantage.
- Showcased how emergent acid-resistant phenotypes outcompete others.
Conclusions:
- The hypoxia-glycolysis-acidosis cycle is essential for the transition from premalignant to invasive cancer.
- Targeting this cycle offers a potential strategy to delay or prevent cancer progression.
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