Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-κB in upregulation of syndecan-1 expression

Abstract

Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-kappaB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-kappaB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-kappaB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-alpha or interleukin-1beta treatment, which can activate NF-kappaB. The amplification of active NF-kappaB and syndecan-1 by tumor necrosis factor-alpha or interleukin-1beta was suppressed by an inhibitor of NF-kappaB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.

Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation

“…There are indications that syndecan-1 transcription can be regulated by the proinflammatory transcription factor nuclear factor-kB, as well as by an FGF-inducible response element located upstream of the syndecan-1 promoter. [27][28][29] Both pathways are relevant in the context of renal transplantation. 30,31 Furthermore, both transforming growth factor-b and EGF have been shown to induce syndecan-1 mRNA expression in vitro, and expression/activation of these factors is enhanced upon renal transplantation, although especially transforming growth factor-b has been associated with fibrosis and EGF with proliferation.…”

Heparan sulfate sulfatase SULF2 regulates PDGFRα signaling and growth in human and mouse malignant glioma

“…SULF2 was considered amplified, if the value of log2(tumor/normal) was greater than or equal to 0.5 (a fold change of tumor copy number vs. normal copy number greater than or equal to 1.41). SAGE expression data included xenograft tumors (tumor numbers 26,5,2,25,7,17,13,18,10,14,19,1,20,16,23,15) and primary tumors (tumor numbers 10, 20, and 23).…”

“…Heparan sulfate proteoglycans (HSPGs) are ubiquitously produced by most animal cells and are a major component of the extracellular environment in normal brain and GBM (16,17). Present on the cell surface and in the ECM, HSPGs play a key role in a number of biological processes based on their ability to bind and regulate the activity of diverse molecules including chemokines and growth factors, such as PDGF, VEGF, and FGF, in many tissues, including the brain (18)(19)(20)(21)(22).…”

Anti‐cancer properties of anthraquinones from rhubarb

“…72 Recently, emodin was reported to suppress the expression of syndecan-1 through inhibiting NF-kB activation in malignant glioma cells, thus capable of blocking the invasion of tumor cells into the surrounding normal brain tissues. 73 Fourth, mainly due to its inhibition on casein kinase II (CKII), emodin shows significant protective effect from angiogenesis and retinal neovascularization. 74 It stabilizes retinal endothelial cell tubes on basement membrane matrix and inhibited secondary sprouting, cell migration, and proliferation.…”