Dexamethasone reduces vascular density and plasminogen activator activity in 9L rat brain tumors

Johannes E.A. Wolff, Christopher Guerin, John Laterra, Joseph Bressler, Ravi R. Indurti, Henry Brem, Gary W. Goldstein

Research output: Contribution to journalArticle

Abstract

Angiogenesis, a process dependent upon perivascular proteolysis, is required for solid tumor growth and is inhibited by certain steroids including glucocorticoids. We examined the relationship between tumor growth and vessel density in experimental rat brain 9L glial tumors following chronic treatment with the glucocorticoid dexamethasone. Tumor growth was inhibitedv by intraperitoneal administration of 3 mg/kg/day dexamethasone. Maximal cross-sectional areas of post-implantation day 9 tumors were 4.6 ± 1.0 mm2 in dexamethasone-treated animals and 17.0 ± 3.4 mm2 in controls (P < 0.01). Microvessel density assessed by laminin immunohistochemistry was 59% lower in dexamethasone-treated tumors (P < 0.01). Plasminogen activator (PA) activity, a proteolytic enzyme related to endothelial migration and vessel growth, was 4.2 ± 0.9 IU/μg protein in dexamethasone-treated tumors and 9.0 ± 1.0 IU/μg protein in control tumors (P < 0.01). Exposure of cultured 9L and central nervous system microvessel endothelial cells to dexamethasone concentrations comparable to those achieved in vivo had no effect on cell growth, but reduced the PA activity of culture supernatant fractions by 78% and 99%, respectively. These findings suggest that inhibition of proteolytic steps involved in vessel growth may underlie, in part, the mechanism by which glucocorticoids decrease brain tumor growth.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalBrain research
Volume604
Issue number1-2
DOIs
StatePublished - Feb 26 1993

Keywords

  • Angiogenesis
  • Endothelial cell
  • Glioma
  • Glucocorticoid
  • Protease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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