Witmer A N, van Blijswijk B C, Dai J, Hofman P, Partanen T A, Vrensen G F, Schlingemann R O
Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
J Pathol. 2001 Nov;195(4):490-7. doi: 10.1002/path.969.
Vascular endothelial growth factor receptor 3 (VEGFR-3, Flt-4), the receptor for vascular endothelial growth factors (VEGFs) C and D, is expressed on lymphatic endothelium and may play a role in lymphangiogenesis. In embryonic life, VEGFR-3 is essential for blood vessel development. The purpose of this study was to investigate whether VEGFR-3 is also involved in blood vessel angiogenesis in the adult. This was studied in human tissues showing angiogenesis and in a model of VEGF-A-induced iris neovascularization in the monkey eye, by the use of immunohistochemistry at the light and electron microscopic level. VEGFR-3 was expressed on endothelium of proliferating blood vessels in tumours. In granulation tissue, staining was observed in the proliferative superficial zone in plump blood vessel sprouts, in the intermediate zone in blood vessels and long lymphatic sprouts, and in the deeper fibrous zone in large lymphatics, in a pattern demonstrating that lymphangiogenesis follows behind blood vessel angiogenesis in granulation tissue formation. At the ultrastructural level, VEGFR-3 was localized in the cytoplasm and on the cell membrane of endothelial cells of sprouting blood vessels and sprouting lymphatics. In monkey eyes injected with VEGF-A, blood vessel sprouts on the anterior iris surface and pre-existing blood vessels in the iris expressed VEGFR-3. In conclusion, these results support a role for VEGFR-3 and its ligands VEGF-C and/or VEGF-D in cell-to-cell signalling in adult blood vessel angiogenesis. The expression of VEGFR-3 in VEGF-A-induced iris neovascularization and in pre-existing blood vessels exposed to VEGF-A suggests that this receptor and possibly its ligands are recruited in VEGF-A-driven angiogenesis.
血管内皮生长因子受体3（VEGFR - 3，Flt - 4）是血管内皮生长因子（VEGF）C和D的受体，在淋巴管内皮细胞上表达，可能在淋巴管生成中发挥作用。在胚胎期，VEGFR - 3对血管发育至关重要。本研究的目的是调查VEGFR - 3是否也参与成人血管生成。通过在光镜和电镜水平使用免疫组织化学方法，在显示血管生成的人体组织以及猴眼VEGF - A诱导的虹膜新生血管模型中对此进行了研究。VEGFR - 3在肿瘤中增殖血管的内皮细胞上表达。在肉芽组织中，在丰满的血管芽的增殖性浅表区域、血管和长淋巴管的中间区域以及大淋巴管的较深纤维区域观察到染色，这种模式表明在肉芽组织形成过程中淋巴管生成落后于血管生成。在超微结构水平，VEGFR - 3定位于发芽血管和发芽淋巴管内皮细胞的细胞质和细胞膜上。在注射VEGF - A的猴眼中，虹膜前表面的血管芽和虹膜中预先存在的血管表达VEGFR - 3。总之，这些结果支持VEGFR - 3及其配体VEGF - C和/或VEGF - D在成人血管生成的细胞间信号传导中发挥作用。VEGFR - 3在VEGF - A诱导的虹膜新生血管以及暴露于VEGF - A的预先存在的血管中的表达表明，该受体及其可能的配体被募集到VEGF - A驱动的血管生成中。
