Scatter factor/hepatocyte growth factor gene transfer increases rat blood-glioma barrier permeability.
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.
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Department of Neurology, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Ranganathan
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Abounader
R
R
Rosen
E
E
Laterra
J
J
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply*; D002199:Capillary Permeability / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005910:Glioma / Q000098:blood supply*; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics*; D008222:Lymphokines / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017228:Hepatocyte Growth Factor; D006735:Horseradish Peroxidase; D019859:Proto-Oncogene Proteins c-met