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Acid-mediated tumor invasion: a multidisciplinary study.

Robert A Gatenby1, Edward T Gawlinski, Arthur F Gmitro

  • 1Departments of Radiology, Applied Mathematics, and Optical Sciences, University of Arizona, Tucson, Arizona 85718, USA. rgatenby@radiology.arizona.edu

Cancer Research
|May 19, 2006
PubMed
Summary
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Altered glucose metabolism in tumors increases acid production, driving invasion into surrounding tissues. This process causes normal cell death and matrix degradation, enabling tumor growth in acidic environments.

Area of Science:

  • Oncology
  • Cancer Biology
  • Biochemistry

Background:

  • Altered glucose metabolism and increased glucose uptake are hallmarks of most cancers, detectable via fluorodeoxyglucose-positron emission tomography (FDG-PET).
  • The acid-mediated tumor invasion hypothesis suggests this metabolic shift fuels cancer progression by acidifying the tumor microenvironment.

Purpose of the Study:

  • To present theoretical and empirical evidence supporting the acid-mediated tumor invasion model.
  • To elucidate the mechanisms by which acidic tumor microenvironments contribute to cancer invasion and host tissue damage.

Main Methods:

  • In silico simulations using mathematical modeling to predict tumor-host interface dynamics.
  • In vivo experiments to validate peritumoral acid gradients, cellular toxicity, and extracellular matrix degradation.

Related Experiment Videos

Main Results:

  • Mathematical models provided testable predictions for tumor-host interface morphology and dynamics.
  • In vivo studies confirmed the existence of peritumoral acid gradients.
  • Evidence of cellular toxicity and extracellular matrix degradation in normal tissue adjacent to acidic tumors was observed.

Conclusions:

  • The acid-mediated tumor invasion model offers a unifying mechanism linking altered glucose metabolism to cancer invasiveness.
  • Tumor cells develop resistance to acidic conditions, facilitating invasion into damaged host tissues.
  • Acid production from altered glucose metabolism is a critical factor in cancer development and spread.