Reduced glioma infiltration in Src-deficient mice

• Published in: Journal of neuro-oncology Vol. 78; no. 1; pp. 19 - 29
• Main Authors: LUND, Caren V, NGUYEN, Mai T. N, OWENS, Geoffrey C, PAKCHOIAN, Andrew J, SHATERIAN, Ashkaun, KRUSE, Carol A, ELICEIRI, Brian P
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.05.2006; Springer Nature B.V
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Blood-Brain Barrier - physiology; Brain Neoplasms - enzymology; Brain Neoplasms - pathology; Capillary Permeability - physiology; Cell Line, Tumor; Cerebrovascular Circulation - physiology; Chemotherapy; Fibrinogen - metabolism; Fluorescent Antibody Technique; Glioma - enzymology; Glioma - pathology; Humans; Immunohistochemistry; Medical sciences; Mice; Mice, Knockout; Microscopy, Confocal; Neoplasm Invasiveness - pathology; Neoplasm Transplantation; Neovascularization, Pathologic - enzymology; Neurology; Pharmacology. Drug treatments; src-Family Kinases - deficiency; Tumors of the nervous system. Phacomatoses; Vascular Endothelial Growth Factor A - metabolism; Animal model; Nervous system diseases; mouse model; VEGF; Rodentia; Malignant tumor; Permeability; Glioblastoma multiforme; Invasion; Malignant glioma; Vertebrata; Mammalia; Mouse; Animal; glioma invasion; Central nervous system disease; Infiltration; vascular permeability
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-005-9068-y

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.