Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells

作     者：Marchiò, S Primo, L Pagano, M Palestro, G Albini, A Veikkola, T Cascone, I Alitalo, K Bussolino, F 

作者机构：Univ Turin Sch Med Dept Genet Biol & Biochem Inst Canc Res & Treatment I-10060 Candiolo Italy Univ Turin Sch Med Dept Biomed Sci & Oncol I-10100 Turin Italy Natl Inst Canc Res I-16100 Genoa Italy Ctr Adv Biotechnol I-16100 Genoa Italy Univ Helsinki Haartman Inst Mol Canc Biol Lab SF-00014 Helsinki Finland 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第39期

页      面：27617-27622页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：细胞分裂/药物作用 细胞 培养的 趋化作用/药物作用 内皮生长因子/药理学 内皮 血管/细胞学 内皮 血管/药物作用 内皮 血管/生理学 小鼠 裸 诱变 定点 磷酰化 受体蛋白质酪氨酸激酶类/遗传学 受体蛋白质酪氨酸激酶类/生理学 受体 细胞表面/遗传学 受体 细胞表面/生理学 重组蛋白质类/药理学 肉瘤 卡波西/病理学 肉瘤 卡波西/病理生理学 移植 异种 肿瘤细胞 培养的 酪氨酸 脐静脉 血管内皮生长因子C 血管内皮生长因子受体3 动物 人类 小鼠 

摘      要：Recent evidence suggesting vascular endothelial growth factor-C (VEGF-C), which is a regulator of lymphatic and vascular endothelial development, raised the question whether this molecule could be involved in Kaposi s sarcoma (KS), a strongly angiogenic and inflammatory tumor often associated with infection by human immunodeficiency virus-1. This disease is characterized by the presence of a core constituted of three main populations of spindle cells, having the features of lymphatic/vascular endothelial cells, macrophagic/ dendritic cells, and of a mixed macrophage endothelial phenotype. In this study we evaluated the biological response of KS cells to VEGF-C, using an immortal cell line derived from a KS lesion (KS IMM), which retains most features of the parental tumor and can induce KS-like sarcomas when injected subcutaneously in nude mice. We show that VEGFR-3, the specific receptor for VEGF-C, is expressed by KS IMM cells grown in vitro and in vivo. In vitro, VEGF-C induces the tyrosine phosphorylation of VEGFR-2, a receptor also for VEGF-A, as well as that of VEGFR-3. The activation of these two receptors in KS IMM cells is followed by a dose-responsive mitogenic and motogenic response. The stimulation of KS IMM cells with a mutant VEGF-C unable to bind and activate VEFGR-2 resulted in no proliferative response and in a weak motogenic stimulation, suggesting that VEGFR-2 is essential in transducing a proliferative signal and cooperates with VEGFR-3 in inducing cell migration. Our data add new insights on the pathogenesis of KS, suggesting that the involvement of endothelial growth factors may not only determine KS-associated angiogenesis, but also play a critical role in controlling KS cell growth and/or migration and invasion.