Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer
Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer
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DOI：
10.1002/ijc.11398
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发表时间：
2003-11-20
影响因子：
6.4
通讯作者：
Gauldie, J
中科院分区：
文献类型：
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作者：
Dabrosin, C;Margetts, PJ;Gauldie, J
血管生成对于肿瘤生长和转移至关重要，也是乳腺癌的重要预后因素。 VEGF 是血管生成的关键因素，与乳腺癌中的肿瘤血管密度相关。雌激素是乳腺癌的另一个关键因素，它会刺激 VEGF； VEGF 基因中的 ERE 已被定义。 VEGF 在细胞外液中具有生物活性，可供内皮细胞利用。 E-2 是否影响细胞外液中 VEGF 水平尚不清楚。我们通过体内瘤内微透析证明，在雌激素依赖性乳腺癌模型中，E-2 治疗可增加肿瘤细胞外 VEGF 水平。此外，肿瘤中 VEGF 的细胞外水平与肿瘤 VEGF 总量呈很强的相关性，这与血浆 VEGF 水平相反。肿瘤细胞外液中测得的 VEGF 93% 源自肿瘤，而循环血浆中的 VEGF 仅 45% 源自肿瘤。我们得出结论，E2 增加细胞外 VEGF，微透析是测量体内局部 VEGF 产生的敏感方法。我们的结果有可能应用于评估人类肿瘤的体内肿瘤特征，以进行个体化癌症治疗。 (C) 2003 年威利利斯。公司
Angiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF; and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E-2 affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E-2 treatment increased tumor extracellular levels of VEGF in an estrogen-dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety-three percent of measured VEGF in the extracellular fluid in the tumor was tumor-derived, while only 45% of VEGF in circulating plasma originated from the tumor. We conclude that E2 increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy. (C) 2003 Wiley-Liss. Inc.