Beta 1 integrin is essential for teratoma growth and angiogenesis.
Beta 1 integrin is essential for teratoma growth and angiogenesis.
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DOI：
10.1083/jcb.139.1.265
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发表时间：
1997-10-06
期刊：
影响因子：
--
通讯作者：
Fässler R
中科院分区：
文献类型：
--
作者：
Bloch W;Forsberg E;Lentini S;Brakebusch C;Martin K;Krell HW;Weidle UH;Addicks K;Fässler R
畸胎瘤是将胚胎干细胞异位注射到小鼠体内后形成的良性肿瘤，含有所有原始生殖层的衍生物。为了研究β1整合素在畸胎瘤形成中的作用，我们比较了正常ES细胞和β1缺失ES细胞诱导的畸胎瘤。注射正常的ES细胞可引起大的畸胎瘤。相反，β1缺失的ES细胞要么不生长，要么形成小畸胎瘤，其平均重量是正常畸胎瘤的5%。β1缺失畸胎瘤的组织学分析显示存在各种分化的细胞，然而，宿主来源的基质细胞的数量比正常畸胎瘤少得多。纤维连接蛋白、I型胶原和巢蛋白表达，但与正常畸胎瘤不同，在β1缺失的畸胎瘤中弥漫性沉积。基底膜存在，但形状不规则，与细胞表面分离。正常畸胎瘤具有内表面光滑的大血管，内含宿主细胞和ES细胞来源的内皮细胞。相比之下，β1缺失的畸胎瘤有松散嵌入结缔组织的小血管。此外，内皮细胞总是来自宿主来源，并形成内表面不规则的血管。尽管畸胎瘤中没有β1缺失的内皮细胞，但β1缺失的ES细胞在体外可以分化为内皮细胞。然而，在β1缺失的拟胚体中，复杂维管系统的形成明显延迟且质量较差。此外，虽然血管内皮生长因子在正常胚状体中诱导内皮细胞的增殖和血管的广泛分支，但在β1缺失的胚状体中却没有作用。
Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of β1 integrin during teratoma formation, we compared teratomas induced by normal and β1-null ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, β1-null ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of β1-null teratomas revealed the presence of various differentiated cells, however, a much lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in β1-null teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal teratomas had large blood vessels with a smooth inner surface, containing both host- and ES cell–derived endothelial cells. In contrast, β1-null teratomas had small vessels that were loosely embedded into the connective tissue. Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface. Although β1- deficient endothelial cells were absent in teratomas, β1-null ES cells could differentiate in vitro into endothelial cells. The formation of a complex vasculature, however, was significantly delayed and of poor quality in β1-null embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in β1-null embryoid bodies.