Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells

Abstract

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.

Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer

“…Our data demonstrating the highest SDC1 serum levels in metastatic BCs support this hypothesis. Third, the heparan sulfate chains located on the extracellular domain of SDC1 are able to bind growth factors such as the pro-angiogenic bFGF and VEGF, thereby inducing angiogenesis [7,8].…”

“…The ectodomain of SDC1 is able to bind a variety of soluble and insoluble ligands, such as extracellular matrix components, growth factors, proteinases and other bioactive molecules and is therefore involved in the regulation of several cellular processes such as cell growth, migration and angiogenesis [3][4][5][6]. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are 2 prominent proangiogenic factors bound by SDC1, which acts as an affinity coreceptor concentrating and presenting ligands to the highaffinity cell surface receptors [7,8].…”

piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma

“…33 In vivo tumor xenograft model Female BALB/C nude mice aged 4-5 weeks were purchased from Beijing Hua Fukang Bioscience Company (Beijing, China) and were housed and monitored in a pathogen-free environment. All animal studies were approved by the Committee on Animals Handling of Huazhong University of Science and Technology.…”

Immunotherapy for multiple myeloma: Current status and future directions

“…It is a significant marker on myeloma cell and is implicated in promoting myeloma cell growth and expansion through increased VEGF receptor-2 (VEGFR-2)-mediated angiogenesis (Lamorte et al, 2012;Witzig et al, 1998). The mAb-drug conjugate nBT062-DM4, now called indatuximab (Biotest AG Dreieich Pharmaceutical Corporation, Germany), has been shown to inhibit tumor growth and promote cytotoxicity of CD-138 positive MM cells both in vitro and in vivo (Ikeda et al, 2009).…”