Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells.
Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells.
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作者：
血管生成被认为是多发性骨髓瘤 (MM) 进展的标志。在本研究中，我们评估了多发性骨髓瘤 (MMEC) 患者骨髓 (BM) 来源的内皮细胞 (EC) 的形态和功能特征。我们发现，与正常骨髓内皮细胞（BMEC）相比，MMEC 的 syndecan-1 表达增加。通过 RNA 干扰技术沉默 syndecan-1 表达会降低体外 EC 的存活、增殖和毛细血管样结构的组织。在体内，在严重联合免疫缺陷小鼠中，syndecan-1 沉默会抑制 MMEC 组织成开放血管。当 syndecan-1 在人脐静脉 EC 和 BMEC 中过度表达时，会诱导体外和体内血管生成作用。对 Syndecan-1 表达沉默的 MMEC 进行流式细胞术分析表明，血管内皮生长因子 (VEGF) 受体 2 (VEGFR-2) 的膜表达降低。免疫沉淀和共聚焦分析显示 VEGFR-2 与 syndecan-1 共定位。 syndecan-1 敲低细胞中 VEGFR-2 核易位的缺失以及从核周定位到回收区室的转变表明 syndecan-1 在调节 VEGFR-2 定位中的作用。这与体外 VEGF 诱导的侵袭和运动减少相关。这些结果表明，syndecan-1 可能通过促进 EC 增殖、存活和调节 VEGF-VEGFR-2 信号传导，促进 MMEC 的高度血管生成表型。
Angiogenesis is considered a hallmark of multiple myeloma (MM) progression. In the present study, we evaluated the morphological and functional features of endothelial cells (ECs) derived from bone marrow (BM) of patients affected by MM (MMECs). We found that MMECs compared with normal BM ECs (BMECs) showed increased expression of syndecan-1. Silencing of syndecan-1 expression by RNA interference technique decreased in vitro EC survival, proliferation and organization in capillary-like structures. In vivo, in severe combined immunodeficient mice, syndecan-1 silencing inhibited MMEC organization into patent vessels. When overexpressed in human umbilical vein ECs and BMECs, syndecan-1 induced in vitro and in vivo angiogenic effects. Flow-cytometric analysis of MMECs silenced for syndecan-1 expression indicated a decreased membrane expression of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2). Immunoprecipitation and confocal analysis showed colocalization of VEGFR-2 with syndecan-1. Absence of nuclear translocation of VEGFR-2 in syndecan-1-knockdown cells together with the shift from perinuclear localization to recycling compartments suggest a role of syndecan-1 in modulation of VEGFR-2 localization. This correlated with an in vitro decreased VEGF-induced invasion and motility. These results suggest that syndecan-1 may contribute to the highly angiogenic phenotype of MMECs by promoting EC proliferation, survival and modulating VEGF–VEGFR-2 signalling.
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