Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors.
Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis lung carcinoma tumors.
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DOI：
10.1007/s10456-010-9195-8
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发表时间：
2011-03
期刊：
影响因子：
9.8
通讯作者：
Li, Lu-Yuan
中科院分区：
文献类型：
--
作者：
Liang, Paulina H.;Tian, Fang;Lu, Yi;Duan, Biyan;Stolz, Donna B.;Li, Lu-Yuan
关键词：
骨髓来源的内皮祖细胞（EPC）在肿瘤新生血管形成中具有重要作用.血管内皮生长抑制因子（VEGI）是肿瘤坏死因子超家族（TNFSF 15）的成员。我们已经证明重组VEGI通过特异性消除增殖的内皮细胞（EC）来抑制肿瘤血管生成。我们在这里报告，治疗荷瘤小鼠与重组血管内皮生长因子导致一个显着减少的人口BM衍生的EPC在肿瘤。我们将绿色荧光蛋白（GFP）转基因小鼠的全骨髓移植到C57 BL/6受体小鼠中，然后接种刘易斯肺癌（LLC）细胞。腹腔内注射重组VEGI导致肿瘤生长的显着抑制和血管密度降低相比，车辆处理的小鼠。肿瘤植入导致外周血中BM衍生的EPC减少，而VEGF治疗导致这种减少的初始延迟。对整个骨髓的分析显示，荷瘤小鼠中Lin−-c-Kit+-Sca-1+造血干细胞（HSC）数量减少;然而，VEGF治疗导致该细胞数量显著增加。此外，VEGF处理的肿瘤中BM来源的EPC的数量明显少于载体处理组，并且VEGF处理的肿瘤中的大多数凋亡细胞是骨髓来源的。这些发现表明，VEGI抑制BM衍生的EPC动员，并通过特异性诱导BM衍生的细胞凋亡来防止它们掺入LLC肿瘤，从而抑制EPC支持的肿瘤血管发生和肿瘤生长。
Bone marrow (BM)-derived endothelial progenitor cells (EPC) have a critical role in tumor neovascularization. Vascular endothelial growth inhibitor (VEGI) is a member of the TNF superfamily (TNFSF15). We have shown that recombinant VEGI suppresses tumor angiogenesis by specifically eliminating proliferating endothelial cells (EC). We report here that treatment of tumor bearing mice with recombinant VEGI leads to a significantly decreased population of BM-derived EPC in the tumors. We transplanted whole bone marrow from green fluorescent protein (GFP) transgenic mice into C57BL/6 recipient mice, which were then inoculated with Lewis lung carcinoma (LLC) cells. Intraperitoneal injection of recombinant VEGI led to significant inhibition of tumor growth and decrease of vasculature density compared to vehicle-treated mice. Tumor implantation yielded a decrease of BM-derived EPC in the peripheral blood, while VEGI-treatment resulted in an initial delay of such decrease. Analysis of the whole bone marrow showed a decrease of Lin−-c-Kit+-Sca-1+ hematopoietic stem cell (HSC) population in tumor bearing mice; however, VEGI-treatment caused a significant increase of this cell population. In addition, the number of BM-derived EPC in VEGI-treated tumors was notably less than that in the vehicle-treated group, and most of the apoptotic cells in the VEGI-treated tumors were of bone marrow origin. These findings indicate that VEGI inhibits BM-derived EPC mobilization and prevents their incorporation into LLC tumors by inducing apoptosis specifically of BM-derived cells, resulting in the inhibition of EPC-supported tumor vasculogenesis and tumor growth.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
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