Reduced glioma infiltration in Src-deficient mice
Caren V Lund1, Mai T N Nguyen, Geoffrey C Owens
1Division of Cancer Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA.
Journal of Neuro-Oncology
|March 23, 2006
Summary
Src deficiency blocks blood-brain barrier leakage, reducing glioma cell invasion. This study reveals Src
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant brain tumors like glioblastoma exhibit significant angiogenesis and blood-brain barrier (BBB) permeability.
- Glioma cell infiltration is a key factor in tumor recurrence after treatment.
- Vascular endothelial growth factor (VEGF)-mediated vascular permeability (VP) drives glioma progression and infiltration.
Purpose of the Study:
- To investigate the role of Src in maintaining BBB integrity during glioma growth.
- To assess the impact of Src deficiency on glioma cell infiltration and BBB permeability.
Main Methods:
- Utilized a Src-deficient (src-/-) mouse model with a 'leakage-resistant phenotype'.
- Orthotopically implanted glioma cells into the brains of control and src-/- mice.
- Evaluated solid tumor growth, glioma cell infiltration, and extracellular matrix (ECM) protein fibrinogen expression.
Main Results:
- Solid tumor growth was comparable between control and src-/- mice.
- Glioma cell infiltration was significantly reduced in src-/- mice.
- Reduced BBB permeability in src-/- mice correlated with decreased glioma invasion.
Conclusions:
- Src plays a critical role in maintaining BBB permeability in the context of brain tumors.
- Targeting Src-mediated BBB leakage offers a potential strategy to inhibit glioma cell invasion.
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