Scatter factor/hepatocyte growth factor gene transfer increases rat blood-glioma barrier permeability

Adam A. Book, Srikanth Ranganathan, Roger Abounader, Eliot Rosen, John Laterra

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant gliomas are associated with a dysfunctional blood-tumor barrier (BTB) that causes substantial morbidity. Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth factor that correlates with glioma malignancy and has several biological properties that suggest a role in enhancing blood-glioma barrier permeability. In this study, we examined the effects of glioma cell SF/HGF expression on BTB permeability to horseradish peroxidase (HRP). Fischer 344 rats bearing intrastriatal 9L tumors engineered to secrete SF/HGF (9L-SF) and SF/HGF-negative control tumors (9L-neo) received intracardiac injections of HRP and were rapidly decapitated. Densitometric analysis of brain sections reacted with diaminobenzidine showed significantly greater extravascular HRP surrounding SF/HGF-secreting tumors than 9L-neo tumors of comparable size (p < 0.05). HRP enzymatic activity associated with striata containing SF/HGF-expressing tumors was 1.6-fold greater than that of striata containing control tumors (p < 0.05). Northern analysis showed that expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) did not differ between 9L-neo and 9L-SF tumors. These data demonstrate that SF/HGF expression by intracerebral glial tumors can enhance BTB permeability independent of changes in VEGF/VPF expression.

Original languageEnglish (US)
Pages (from-to)173-180
Number of pages8
JournalBrain research
Volume833
Issue number2
DOIs
StatePublished - Jul 3 1999

Keywords

  • Blood-brain barrier
  • Brain tumor
  • Edema
  • Glioma
  • Horseradish peroxidase
  • Vascular endothelial growth factor

ASJC Scopus subject areas

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

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