Reduced tumor growth and angiogenesis in endoglin-haploinsufficient mice
Reduced tumor growth and angiogenesis in endoglin-haploinsufficient mice
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DOI：
10.1159/000097040
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发表时间：
2007-01-01
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影响因子：
--
通讯作者：
Lopez-Novoa, Jose M.
中科院分区：
文献类型：
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作者：
Duwel, Annette;Eleno, Nelida;Lopez-Novoa, Jose M.
内皮糖蛋白是一种转化生长因子-β（1）（TGF-β（1））辅助受体，在肿瘤血管中高度表达。为了研究内皮糖蛋白在肿瘤生长和血管生成中的作用，我们通过皮下注射10（6）个刘易斯肺癌（3LL）细胞，在内皮糖蛋白杂合小鼠（Eng +/-）和它们的对照同窝小鼠（Eng +/+）中诱导高度血管化的肿瘤。注射后9天，取出肿瘤并称重。毛细血管密度（CD31免疫组化），血红蛋白含量和血管细胞粘附分子-1（VCAM-1）的表达来评估肿瘤血管化。采用激光多普勒技术测量肿瘤血流灌注率。Western blot检测缺氧诱导因子（HIF）、内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）的表达。通过对肿瘤组织ATP含量的测定，推测肿瘤组织存在有氧代谢和氧依赖性。与Eng +/+同窝仔相比，Eng +/-中的肿瘤重量、毛细血管密度、血红蛋白和VCAM-1降低约30%。与Eng +/+小鼠相比，Eng +/+小鼠中eNOS和磷酸化eNOS的蛋白水平显著降低。与Eng +/+相比，Eng +/-中HIF表达略有降低，而VEGF水平略有增加。两种小鼠的肿瘤组织ATP和ADP水平相似。这些数据表明内皮糖蛋白在肿瘤新生血管生成中起主要作用。版权所有（c）2007 S. Karger AG，巴塞尔。
Endoglin is a transforming growth factor-beta(1) (TGF-beta(1)) accessory receptor which is highly expressed in tumor vessels. To study the role of endoglin in tumor growth and angiogenesis we induced a highly vascularized tumor in mice heterozygous for endoglin (Eng+/-) and in their control littermates (Eng+/+) by injecting 10(6) Lewis lung carcinoma (3LL) cells subcutaneously. Nine days after injection, the tumor was removed and weighed. Capillary density (CD31 immunohistochemistry), hemoglobin content and vascular cell adhesion molecule-1 (VCAM-1) expression were used to assess tumor vascularization. Tumor perfusion rate was measured by laser-Doppler technique. Expression of the hypoxia-inducible factor (HIF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were determined by Western blot analysis. The aerobic metabolism and oxygen dependency were inferred from the measurement of ATP in tumoral tissue. Tumor weight, capillary density, hemoglobin and VCAM-1 were reduced by about 30% in Eng+/- compared to Eng+/+ littermates. The protein levels of eNOS and phosphorylated eNOS were significantly reduced in Eng+/+ compared to Eng+/+ mice. HIF expression was slightly reduced whereas VEGF level was slightly increased in Eng+/- compared to Eng+/+. Tumor tissue levels of ATP and ADP were similar in both types of mice. These data demonstrate that endoglin plays a major role in tumor neoangiogenesis. Copyright (c) 2007 S. Karger AG, Basel.