Journal
JOURNAL OF NEURO-ONCOLOGY
Volume 78, Issue 1, Pages 19-29Publisher
SPRINGER
DOI: 10.1007/s11060-005-9068-y
Keywords
glioblastoma multiforme; glioma invasion; mouse model; vascular permeability; VEGF
Categories
Funding
- NHLBI NIH HHS [R01 HL073396, R01 HL073396-07] Funding Source: Medline
- NINDS NIH HHS [R21 NS046463] Funding Source: Medline
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Malignant brain tumors, such as glioblastoma, are characterized by extensive angiogenesis and permeability of the blood-brain barrier (BBB). The infiltration of glioma cells away from the primary tumor mass is a pathological characteristic of glial tumors. The infiltrating tumor cells represent a significant factor in tumor recurrence following surgical debulking, radiation, and chemotherapy treatments. Vascular endothelial growth factor (VEGF)-mediated vascular permeability (VP) has been associated with the progression of glioma tumor growth and infiltration into surrounding normal brain parenchyma. While VEGF induces a robust VP response in control mice (src(+/+) or src(+/-)), the VP response is blocked in src(-/-) mice that demonstrate a 'leakage-resistant phenotype' in the brain. We used the Src deficient mouse model to determine the role of Src in the maintenance of the BBB following orthotopic implantation and growth of glioma cells in the brain. Although solid tumor growth was the same in control and src(-/-) mice, the infiltrating component of glioma growth was reduced in src(-/-) mice. Characterization of the expression and localization of the extracellular matrix (ECM) protein fibrinogen was evaluated to determine the effect of a Src-mediated VP defect in the host compartment. These studies indicate that the reduced VP of host brain blood vessels of src(-/-) mice mediates a reduction in glioma cell invasion in a mouse brain tumor xenograft model.
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