Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin.

Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin.
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发表时间:
2002-11
期刊:
影响因子:
11.2
通讯作者:
Chan Woo Kim;Hwan Myung Lee;T. Lee;Chulhun Kang;H. Kleinman;Y. Gho
Chan Woo Kim;Hwan Myung Lee;T. Lee;Chulhun Kang;H. Kleinman;Y. Gho
中科院分区:
医学1区
文献类型:
--
作者:
Chan Woo Kim;Hwan Myung Lee;T. Lee;Chulhun Kang;H. Kleinman;Y. Gho

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活跃生长的肿瘤细胞在体内和体外都将膜囊泡脱落到细胞外环境中。来自肿瘤细胞的细胞外膜囊泡含有存在于这些细胞上的大多数表面抗原和蛋白酶。它们促进肿瘤逃避免疫监视并促进肿瘤细胞侵袭。在这里,我们表明,肿瘤膜囊泡刺激一个额外的重要活动,肿瘤的生长和转移,促进内皮细胞迁移,入侵,和管的形成,并诱导体内新血管形成。我们的数据表明,肿瘤囊泡是参与肿瘤诱导的血管生成的多种效应物之一。热处理的囊泡和囊泡的脂质提取物也诱导内皮细胞迁移和体内血管生成。我们确定鞘磷脂作为囊泡诱导的内皮细胞迁移,管形成和新血管形成的活性成分。结合先前报道的结果,我们的数据表明脱落的肿瘤囊泡通过促进血管生成、肿瘤侵袭和免疫逃逸在肿瘤生长和转移中发挥多种作用。
Actively growing tumor cells shed membrane vesicles into the extracellular milieu both in vivo and in vitro. Extracellular membrane vesicles from tumor cells contain most surface antigens and proteases present on these cells. They facilitate the escape of tumors from immune surveillance and promote tumor cell invasion. Here, we demonstrate that tumor membrane vesicles stimulate an additional important activity for tumor growth and metastasis by promoting endothelial cell migration, invasion, and tube formation, and inducing in vivo neovascularization. Our data show that tumor vesicles are one of the multiple effectors involved in tumor-induced angiogenesis. Heat-treated vesicles and lipid extracts from the vesicles also induce endothelial cell migration and in vivo angiogenesis. We identify sphingomyelin as the active component for vesicle-induced endothelial cell migration, tube formation, and neovascularization. Together with previously reported results, our data demonstrate that shed tumor vesicles play multiple roles in tumor growth and metastasis by promoting angiogenesis, tumor invasion, and immune escape.