Kaipainen A, Korhonen J, Mustonen T, van Hinsbergh V W, Fang G H, Dumont D, Breitman M, Alitalo K
Molecular/Cancer Biology Laboratory, University of Helsinki, Finland.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3566-70. doi: 10.1073/pnas.92.8.3566.
We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.
我们最近克隆了人类fms样酪氨酸激酶4基因FLT4，其蛋白质产物与两种血管内皮生长因子受体FLT1和KDR/FLK1相关。在此，我们通过原位杂交分析了FLT4在小鼠胚胎发育过程中和成人组织中的表达情况。FLT4 mRNA信号最早在8.5天交配后（p.c.）胚胎头部间充质、主静脉的成血管细胞以及胚外尿囊中被检测到。在12.5天p.c.胚胎中，FLT4信号标记了发育中的静脉和假定的淋巴管内皮，但动脉内皮为阴性。在发育后期，FLT4 mRNA局限于不含红细胞的血管丛，代表发育中的淋巴管。在成人组织中，只有淋巴管内皮和一些高内皮微静脉表达FLT4 mRNA。在转移性淋巴结的淋巴窦和淋巴管瘤中表达增加。我们的结果表明，FLT4是成人组织中淋巴管和一些高内皮微静脉的标志物。它们也支持淋巴管起源于静脉的理论。
