α6-Integrin is required for the adhesion and vasculogenic potential of hemangioma stem cells.
α6-Integrin is required for the adhesion and vasculogenic potential of hemangioma stem cells.
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血管瘤干细胞的粘附和血管生成潜力需要α6-整合素。
DOI：
10.1002/stem.1539
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发表时间：
2014-03
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：
Smadja, David M.;Guerin, Coralie L.;Boscolo, Elisa;Bieche, Ivan;Mulliken, John B.;Bischoff, Joyce
婴儿血管瘤是婴儿期最常见的肿瘤。血管瘤干细胞（HemSC）是从IH CD 133+细胞分离的间充质亚群。HemSC可分化为内皮细胞和周细胞/平滑肌细胞，并在免疫缺陷小鼠中注射时形成血管网络。α6-整合素亚基与胶质母细胞瘤干细胞的致瘤性以及造血、内皮和间充质祖细胞的归巢特性有关。因此，我们研究了α6-整合素在HemSC中的可能功能。我们通过RT-qPCR和流式细胞术记录了IH肿瘤标本和HemSC中α6-整合素的表达。我们检测了阻断或沉默α6-整合素对HemSC体外粘附和增殖特性以及体内血管生成和归巢特性的影响。在培养的HemSC中靶向α6-整合素抑制与层粘连蛋白的粘附，但对增殖没有影响。在α6-整合素siRNA转染的HemSC中，Matrigel植入物中的血管形成能力和静脉内递送后的肝归巢显著降低。α6-整合素是HemSC粘附于层粘连蛋白、体内血管形成和归巢至肝脏所必需的。因此，我们揭示了α6整合素在HemSC血管生成特性中的重要作用。我们的研究结果表明，α6-整合素表达的血管干细胞可能是一个新的目标，抗血管瘤治疗。
Infantile hemangioma (IH) is the most common tumor of infancy. Hemangioma stem cells (HemSC) are a mesenchymal subpopulation isolated from IH CD133+ cells. HemSC can differentiate into endothelial and pericyte/smooth muscle cells and form vascular networks when injected in immune-deficient mice. α6-Integrin subunit has been implicated in the tumorgenicity of glioblastoma stem cells and the homing properties of hematopoietic, endothelial and mesenchymal progenitor cells. Therefore, we investigated the possible function(s) of α6-integrin in HemSC. We documented α6-integrin expression in IH tumor specimens and HemSC by RT-qPCR and flow cytometry. We examined the effect of blocking or silencing α6-integrin on the adhesive and proliferative properties of HemSCin vitro and the vasculogenic and homing properties of HemSCin vivo. Targeting α6-integrin in cultured HemSC inhibited adhesion to laminin but had no effect on proliferation. Vessel-forming ability in Matrigel implants and hepatic homing after intravenous delivery were significantly decreased in α6-integrin siRNA transfected HemSC. α6-Integrin is required for HemSC adherence to laminin, vessel formation in vivo and for homing to the liver. Thus, we uncovered an important role for α6 integrin in the vasculogenic properties of HemSC. Our results suggest that α6-integrin expression on HemSC could be a new target for anti-hemangioma therapy.
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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：
2.4
作者：
Kulungowski, Ann M.;Alomari, Ahmad I.;Fishman, Steven J.
通讯作者：
Fishman, Steven J.
影响因子：
3.5
作者：
Pulkkinen, L;Kimonis, VE;Uitto, J
通讯作者：
Uitto, J
影响因子：
6.4
作者：
Cariati, Massimiliano;Naderi, Ali;Purushotham, Anand D.
通讯作者：
Purushotham, Anand D.
影响因子：
23.9
作者：
Lathia JD;Gallagher J;Heddleston JM;Wang J;Eyler CE;Macswords J;Wu Q;Vasanji A;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN