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【Cancer research】17β雌二醇动员骨髓来源的内皮祖
17β-Estradiol Mobilizes Bone Marrow–Derived Endothelial Progenitor Cells to Tumors
Robert Suriano1, Devyani Chaudhuri1, Raja Singh Johnson2, Erin Lambers2, Badithe T. Ashok1, Raj Kishore2 and Raj K. Tiwari1
Key Words: Tumor biology • breast cancer • cell mobilization • progenitor endothelial cells • conditioned media
Neovascularization is critical for tumor growth and development. The cellular mediators for this process are yet to be defined. We discovered that bone marrow–derived endothelial progenitor cells (BM-EPC), having the phenotype (CD133+, CD34+, VEGFR-2+), initiate neovascularization in response to TG1-1 mammary cells implanted in the inguinal mammary gland of Tie-2 GFP transgenic mice. The fluorescence tag allowed for tracing the migration of green fluorescent protein–tagged endothelial progenitor cells to tumor tissues. We discovered that 17-β estradiol supplementation of ovariectomized mice significantly enhanced BM-EPC–induced neovascularization and secretion of angiogenic factors within the tumor microenvironment. Cell-based system analyses showed that estrogen-stimulated BM-EPCs secreted paracrine factors which enhanced TG1-1 cell proliferation and migration. Furthermore, TG1-1 cell medium supplemented with estrogen-induced BM-EPC mediated tubulogenesis, which was an experimental in vivo representation of the neovasculature. Our data provide evidence of BM-EPC mammary tumor cell interactions and identify a novel cellular mediator of tumor progression that can be exploited clinically. [Cancer Res 2008;68(15):6038–42] 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 17β-Estradiol Mobilizes Bone Marrow–Derived Endothelial Progenitor Cells to Tumors
17β-雌二醇动员骨髓源性内皮祖细胞迁移至肿瘤组织
Robert Suriano1, Devyani Chaudhuri1, Raja Singh Johnson2, Erin Lambers2, Badithe T. Ashok1, Raj Kishore2 and Raj K. Tiwari1
Key Words: Tumor biology • breast cancer • cell mobilization • progenitor endothelial cells • conditioned media
关键词：肿瘤生物学；乳腺癌；细胞活化；内皮祖细胞；环境介质
Neovascularization is critical for tumor growth and development. The cellular mediators for this process are yet to be defined. We discovered that bone marrow–derived endothelial progenitor cells (BM-EPC), having the phenotype (CD133+, CD34+, VEGFR-2+), initiate neovascularization in response to TG1-1 mammary cells implanted in the inguinal mammary gland of Tie-2 GFP transgenic mice. The fluorescence tag allowed for tracing the migration of green fluorescent protein–tagged endothelial progenitor cells to tumor tissues. We discovered that 17-β estradiol supplementation of ovariectomized mice significantly enhanced BM-EPC–induced neovascularization and secretion of angiogenic factors within the tumor microenvironment. Cell-based system analyses showed that estrogen-stimulated BM-EPCs secreted paracrine factors which enhanced TG1-1 cell proliferation and migration. Furthermore, TG1-1 cell medium supplemented with estrogen-induced BM-EPC mediated tubulogenesis, which was an experimental in vivo representation of the neovasculature. Our data provide evidence of BM-EPC mammary tumor cell interactions and identify a novel cellular mediator of tumor progression that can be exploited clinically. [Cancer Res 2008;68(15):6038–42]
肿瘤血管形成对肿瘤生长和发展起着至关重要的作用。在这一过程中的细胞介质仍未完全明确。我们发现细胞表型为(CD133+, CD34+, VEGFR-2+)的骨髓源性内皮细胞祖细胞可以激发种植于Tie-2 GFP转基因大鼠腹股沟区的TG1-1乳腺细胞的血管新生。通过免疫应光标记法可以追踪到绿色荧光蛋白标记的内皮祖细胞迁移至肿瘤组织。我们同样发现，给切除卵巢的大鼠补充17β-雌二醇可以显著加强骨髓源性内皮细胞祖细胞形成新生血管这一过程，并增加肿瘤微环境中血管形成刺激因子的产生。细胞水平的分析显示雌二醇可以刺激骨髓源性内皮细胞祖细胞通过旁分泌作用刺激TG1-1增生和迁移。而且，TG1-1微环境存在雌二醇诱导的骨髓源性内皮细胞祖细胞可以增加血管形成，而这是体内血管形成的一个代表。
我的研究结果为骨髓源性内皮细胞祖细胞与乳腺肿瘤细胞的相互作用提供了新的证据，并可以据此确定一个临床可以检测的肿瘤形成过程中新的细胞介质 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-05-28 05:14
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