Reduced glioma infiltration in Src-deficient mice
Reduced glioma infiltration in Src-deficient mice
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DOI：
10.1007/s11060-005-9068-y
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发表时间：
2006-05-01
影响因子：
3.9
通讯作者：
Eliceiri, Brian P.
中科院分区：
文献类型：
--
作者：
Lund, Caren V.;Nguyen, Mai T. N.;Eliceiri, Brian P.
恶性脑肿瘤，如胶质母细胞瘤，其特征在于广泛的血管生成和血脑屏障（BBB）的渗透性。胶质瘤细胞远离原发肿瘤块的浸润是胶质瘤的病理特征。浸润性肿瘤细胞是手术减积、放疗和化疗后肿瘤复发的重要因素。血管内皮生长因子（VEGF）介导的血管通透性（VP）与胶质瘤生长和浸润周围正常脑实质的进展有关。虽然VEGF在对照小鼠（src（+/+）或src（+/-））中诱导了强有力的VP应答，但在大脑中表现出“抗渗漏表型”的src（-/-）小鼠中VP应答被阻断。我们使用Src缺陷的小鼠模型来确定Src在原位植入和脑胶质瘤细胞生长后维持BBB中的作用。虽然实体瘤生长在对照组和src（-/-）小鼠中是相同的，但神经胶质瘤生长的浸润成分在src（-/-）小鼠中减少。评价细胞外基质（ECM）蛋白纤维蛋白原的表达和定位的表征，以确定Src介导的VP缺陷在宿主隔室中的影响。这些研究表明src（-/-）小鼠宿主脑血管的VP降低介导了小鼠脑肿瘤异种移植模型中胶质瘤细胞侵袭的减少。
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.