Estradiol-mediated tumor neo-vascularization.

Estradiol-mediated tumor neo-vascularization.
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DOI:
10.3892/ol.2011.283
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发表时间:
2011-05
期刊:
影响因子:
2.9
通讯作者:
S. Rajoria;R. Suriano;Y. Wilson;A. George;J. Geliebter;S. Schantz;R. Tiwari
S. Rajoria;R. Suriano;Y. Wilson;A. George;J. Geliebter;S. Schantz;R. Tiwari
中科院分区:
医学4区
文献类型:
--
作者:
S. Rajoria;R. Suriano;Y. Wilson;A. George;J. Geliebter;S. Schantz;R. Tiwari

文献摘要

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新生血管形成是肿瘤生长和转移的关键,可能由骨髓来源的内皮祖细胞(BM-EPCs)启动。这些细胞主要存在于骨髓中,并在炎症、组织损伤和肿瘤部位募集。负责募集BM-EPCs和新血管形成的组织特异性因素是深入研究的主题。使用Tek/绿色荧光蛋白(GFP)转基因小鼠的骨髓细胞,我们分析了雌激素对BM-EPCs向雌激素补充和非雌激素补充的卵巢切除小鼠原位植入癌细胞的动员作用。供体骨髓细胞是独特的,因为它们被荧光标记,允许跟踪它们向肿瘤组织的迁移。结果显示,与假注射相比,GFP + BM-EPCs掺入肿瘤血管系统内。值得注意的是,雌激素补充增强了BM-EPCs向肿瘤部位的动员。这种升高表明雌激素可能通过诱导BM-EPCs的动员来影响肿瘤新生血管形成。了解和表征参与雌激素诱导的BM-EPCs动员的机制可以作为递送生物分子的“特洛伊木马”,其可以破坏肿瘤血管生成并诱导肿瘤细胞的靶向杀伤。
Neo-vascularization is essential for tumor growth and metastasis and is presumably initiated by bone marrow-derived endothelial progenitor cells (BM-EPCs). These cells predominantly reside in the bone marrow and are recruited at sites of inflammation, tissue damage and tumors. The tissue-specific factors responsible for recruitment of BM-EPCs and neo-vascularization are the subject of intense investigation. Using bone marrow cells from Tek/green fluorescent protein (GFP) transgenic mice, we analyzed the effect of estrogen on the mobilization of BM-EPCs to orthotopically implanted cancer cells in estrogen- and non-estrogen-supplemented ovariectomized mice. The donor marrow cells were unique as they were fluorescently tagged, allowing for the tracking of their migration to the tumor tissues. Results showed that GFP + BM-EPCs were incorporated within the tumor vasculature in comparison to the sham injections. Notably, estrogen supplementation enhanced the mobilization of BM-EPCs to the tumor site. This elevation shows that estrogen may affect tumor neo-vascularization by inducing the mobilization of BM-EPCs. Understanding and characterizing the mechanism involved in the estrogen-induced mobilization of BM-EPCs may serve as a 'Trojan horse' in the delivery of bio-molecules that may disrupt tumor vasculogenesis and induce the targeted killing of tumor cells.