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Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability

Masako Nozaki1, Masanobu Yoshikawa, Kunihiko Ishitani

  • 1Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa, Japan. tokai-irc@tokai-u.jp

The Keio Journal of Medicine
|April 9, 2010
PubMed

Insights

Pranlukast effectively inhibits tumor cell migration in both brain and peripheral capillaries, while montelukast only shows efficacy in peripheral capillaries. This research highlights potential therapeutic applications for these cysteinyl leukotriene receptor antagonists in cancer metastasis.

Area of Science:

  • Pharmacology
  • Oncology
  • Neuroscience

Background:

  • Tumor cell migration is a critical step in cancer metastasis.
  • Cysteinyl leukotriene receptor antagonists (LTRAs) are used to treat asthma.
  • The role of LTRAs in inhibiting tumor cell extravasation is not fully understood.

Purpose of the Study:

  • To investigate the potential of pranlukast and montelukast in preventing tumor cell migration through cerebral and peripheral capillaries.
  • To compare the efficacy of pranlukast and montelukast in inhibiting cancer cell extravasation.

Main Methods:

  • Tumor cell migration through brain capillaries was studied in rats using RCN9 cells and arachidonic acid administration.
  • Cancer cell extravasation in peripheral capillaries was assessed using a Lewis lung carcinoma metastasis model in mice.
  • Rats and mice were treated with pranlukast or montelukast.

Main Results:

  • Arachidonic acid increased fluid volume and cell counts in the brain capillaries.
  • Pranlukast, but not montelukast, reduced brain capillary fluid volume and inhibited cell extravasation when administered prior to arachidonic acid.
  • Both pranlukast and montelukast prevented tumor metastasis and prolonged survival in the peripheral capillary model.

Conclusions:

  • Pranlukast inhibits tumor cell migration through both brain and peripheral capillaries.
  • Montelukast inhibits tumor cell migration only in peripheral capillaries.
  • These findings suggest differential effects of LTRAs on tumor cell extravasation in different vascular beds.

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