c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro
c-fos-induced growth factor/vascular endothelial growth factor D induces angiogenesis in vivo and in vitro
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DOI：
10.1073/pnas.96.17.9671
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发表时间：
1999-08-17
影响因子：
11.1
通讯作者：
Oliviero, S
中科院分区：
文献类型：
--
作者：
Marconcini, L;Marchio, S;Oliviero, S
C-fos诱导生长因子/血管内皮生长因子D(FIGF/VEGF-D)是血管内皮生长因子家族的一种分泌型因子，与血管和淋巴管受体VEGFR-2和VEGFR-3结合，本文报道FIGF/VEGF-D是体内兔角膜中一种强有力的血管生成因子，且呈剂量依赖性。在体外，FIGF/VEGF-D诱导原代人脐静脉内皮细胞(HUVECs)和Kaposi肉瘤病变永生细胞系(KS-IMM)VEGFR-2和VEGFR-3的酪氨酸磷酸化。FIGF/VEGF-D处理人脐静脉内皮细胞可诱导细胞生长，并呈剂量依赖性。FIGF/VEGF-D还诱导HUVEC延长和分支，形成三维基质中广泛的毛细血管样索网络。在KS-IMM细胞中，FIGF/VEGF-D处理导致剂量依赖的有丝分裂和运动生成活性。结合以往关于FIGF/VEGF-D的表达受核癌基因c-fos控制的研究，我们的数据揭示了核癌基因与血管生成之间的联系，提示FIGF/VEGF-D可能在肿瘤细胞的生长和侵袭中发挥关键作用。
c-fos-induced growth factor/vascular endothelial growth factor D (Figf/Vegf-D) is a secreted factor of the VEGF family that binds to the vessel and lymphatic receptors VEGFR-2 and VEGFR-3, Here,ve report that Figf/Vegf-D is a potent angiogenic factor in rabbit cornea in vivo in a dose-dependent manner. In vitro Figf/Vegf-D induces tyrosine phosphorylation of VEGFR-2 and VEGFR-3 in primary human umbilical cord vein endothelial cells (HUVECs) and in an immortal cell line derived from Kaposi's sarcoma lesion (KS-IMM). The treatment of HUVECs with Figf/Vegf-D induces dose-dependent cell growth. Figf/VEGF-D also induces HUVEC elongation and branching to form an extensive network of capillary-like cords in three-dimensional matrix. In KS-IMM cells Figf/Vegf-D treatment results in dose-dependent mitogenic and motogenic activities. Taken together with the previous observations that Figf/Vegf-D expression is under the control of the nuclear oncogene c-fos, our data uncover a link between a nuclear oncogene and angiogenesis, suggesting that Figf/Vegf-D may play a critical role in tumor cell growth and invasion.