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Related Experiment Videos

Morphologic instability and cancer invasion.

Vittorio Cristini1, Hermann B Frieboes, Robert Gatenby

  • 1Department of Biomedical Engineering, University of California, Irvine, California 92697-2715, USA. cristini@math.uci.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 6, 2005
PubMed
Summary

Microenvironmental gradients in solid tumors can drive invasive growth. Suppressing tumor invasion requires homogeneous nutrient supply and therapies that enhance cell adhesion, not just reduce vascular density.

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Area of Science:

  • Oncology
  • Tumor Microenvironment
  • Cancer Biology

Background:

  • Solid tumors create oxygen and nutrient gradients due to high consumption and variable vascularization.
  • These gradients lead to intratumoral hypoxia, acidosis, and heterogeneous cell proliferation and migration.
  • Hypothesis: Microenvironmental substrate gradients drive tumor morphologic instability and invasion.

Purpose of the Study:

  • To investigate the role of microenvironmental substrate gradients in driving tumor morphologic instability and invasion.
  • To explore mechanisms that suppress or promote tumor invasion.
  • To evaluate the impact of antiangiogenic therapy on tumor morphology and invasiveness.

Main Methods:

  • Computer simulations were employed to model tumor behavior.

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  • In vitro experiments were conducted to validate simulation findings.

    • Main Results:

    • Homogeneous oxygen and nutrient supply suppressed morphologic instability by reducing gradients and increasing cell adhesion.
    • A functional tumor microvasculature promotes compact, non-infiltrating tumor shapes by minimizing gradients.
    • Antiangiogenic therapy, by increasing heterogeneity, may paradoxically promote invasion, even with tumor shrinkage.

    Conclusions:

    • Therapies solely reducing vascular density may increase invasive behavior.
    • The model explains variable antiangiogenic therapy outcomes.
    • Combined strategies normalizing vasculature and increasing cell adhesion are proposed for consistent success in suppressing invasion.