Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells.
Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells.
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DOI：
10.1002/stem.1841
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发表时间：
2015-01
期刊：
影响因子：
5.2
通讯作者：
Bischoff, Joyce
中科院分区：
文献类型：
--
作者：
Huang, Lan;Nakayama, Hironao;Klagsbrun, Michael;Mulliken, John B.;Bischoff, Joyce
内皮葡萄糖转运蛋白 1 (GLUT1) 是婴儿血管瘤 (IH)（一种婴儿血管肿瘤）的明确诊断标志物。迄今为止，IH 中的 GLUT1 阳性内皮细胞尚未被量化，也没有直接分离和研究。我们从 IH 标本中分离了 GLUT1 阳性和 GLUT1 阴性内皮细胞，并表征了它们的增殖、分化以及对普萘洛尔（IH 一线疗法）和雷帕霉素（一种 mTOR 通路抑制剂，用于治疗越来越广泛的增殖性疾病）的反应。尽管使用抗 GLUT1 磁珠选择的新鲜分离的 GLUT1 阳性细胞表达内皮标记物 CD31、VE-钙粘蛋白和 VEGFR2，但它们在培养三周后转化为间充质表型。相反，GLUT1阴性内皮细胞在体外表现出稳定的内皮表型。 GLUT1选择的细胞在作为单细胞铺板时具有克隆形成性，并且可以被诱导再分化为内皮细胞、周细胞/平滑肌细胞或脂肪细胞，表明干细胞样表型。这些数据表明，尽管GLUT1阳性内皮细胞在肿瘤中作为真正的内皮细胞出现并发挥功能，但它们显示出兼性干细胞的特性。用雷帕霉素预处理4天显着减缓了GLUT1选择的细胞的增殖，而普萘洛尔预处理则没有效果。这些结果首次揭示了婴儿血管瘤中 GLUT1 阳性内皮细胞的兼性性质。
Endothelial glucose transporter 1 (GLUT1) is a definitive and diagnostic marker for infantile hemangioma (IH), a vascular tumor of infancy. To date, GLUT1-positive endothelial cells in IH have not been quantified nor directly isolated and studied. We isolated GLUT1-positive and GLUT1-negative endothelial cells from IH specimens and characterized their proliferation, differentiation and response to propranolol, a first-line therapy for IH, and to rapamycin, an mTOR pathway inhibitor used to treat an increasingly wide array of proliferative disorders. Although freshly isolated GLUT1-positive cells, selected using anti-GLUT1 magnetic beads, expressed endothelial markers CD31, VE-Cadherin and VEGFR2, they converted to a mesenchymal phenotype after three weeks in culture. In contrast, GLUT1-negative endothelial cells exhibited a stable endothelial phenotype in vitro. GLUT1-selected cells were clonogenic when plated as single cells and could be induced to re-differentiate into endothelial cells, or into pericyte/smooth muscle cells or into adipocytes, indicating a stem cell-like phenotype. These data demonstrate that, although they appear and function in the tumor as bona fide endothelial cells, the GLUT1-positive endothelial cells display properties of facultative stem cells. Pretreatment with rapamycin for 4 days significantly slowed proliferation of GLUT1-selected cells, whereas propranolol pretreatment had no effect. These results reveal for the first time the facultative nature of GLUT1-positive endothelial cells in infantile hemangioma.
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DOI：
10.1056/nejmoa0903036
发表时间：
2010-03-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greenberger S;Boscolo E;Adini I;Mulliken JB;Bischoff J
通讯作者：
Bischoff J
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
10.5
作者：
Kim, Jiha;Oh, Won-Jong;Gu, Chenghua
通讯作者：
Gu, Chenghua
影响因子：
1.5
作者：
Kaylani, Samer;Theos, Amy J.;Pressey, Joseph G.
通讯作者：
Pressey, Joseph G.
影响因子：
50.3
作者：
Dudley AC;Khan ZA;Shih SC;Kang SY;Zwaans BM;Bischoff J;Klagsbrun M
通讯作者：
Klagsbrun M