Proteoglycan expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines

Abstract

The involvement of proteoglycans (PGs) in EBV-host interactions and lymphomagenesis remains poorly investigated. In this study, expression of major proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, aggrecan, NG2, serglycin, decorin, biglycan, lumican, CD44), heparan sulphate (HS) metabolic system (EXT1/2, NDST1/2, GLCE, HS2ST1, HS3ST1/2, HS6ST1/2, SULF1/2, HPSE) and extracellular matrix (ECM) components (collagen 1A1, fibronectin, elastin) in primary B cells and EBV carrying cell lines with different phenotypes, patterns of EBV-host cell interaction and viral latency stages (type I-III) was investigated. Primary B cells expressed a wide repertoire of PGs (dominated by serglycin and CD44) and ECM components. Lymphoblastoid EBV+ B cell lines (LCLs) showed specific PG expression with down-regulation of CD44 and ECM components and up-regulation of serglycin and perlecan/HSPG2. For Burkitt's lymphoma cells (BL), serglycin was down-regulated in BL type III cells and perlecan in type I BL cells. The biosynthetic machinery for HS was active in all cell lines, with some tendency to be down-regulated in BL cells. 5′-aza-dC and/or Trichostatin A resulted in transcriptional upregulation of the genes, suggesting that low expression of ECM components, proteoglycan core proteins and HS biosynthetic system is due to epigenetic suppression in type I cells. Taken together, our data show that proteoglycans are expressed in primary B lymphocytes whereas they are not or only partly expressed in EBV-carrying cell lines, depending on their latency type program.

Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

“…Our results on the decreased overall transcriptional activity of the HS biosynthetic system in glioblastoma ( Figure 1 ) are in good agreement with the TCGA-based analysis. They also correlate with and supplement the data on the tissue specificity of changes in the transcriptional activity of the HS biosynthetic system in various cancer types; a significant suppression of this system has been shown in human prostate tumours [ 33 ] and Burkitt’s lymphoma cells [ 34 ], although its activity was not changed in breast and colon tumours [ 19 , 35 ]. At the same time, there are some contrasts between our results and the earlier published data for individual genes.…”

Serglycin in Quiescent and Proliferating Primary Endothelial Cells

“…Furthermore, high levels of serglycin were demonstrated in nasopharyngeal carcinoma cells, with higher levels in clones with increased metastatic potential and also, with higher motility [ 26 ]. Recently, serglycin expression was related to cancer aggressivity both in tumor and stroma [ 54 , 55 ].…”

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

“…The CS chains bind several ligands and receptors, and CSPGs thereby act as major factors in tumor growth and invasion (18-23). EBV-positive BL-derived cell lines have recently been shown to express a broad repertoire of CSPGs (24). However, the functional significance of CSPG expression in BL is still largely unknown.…”

“…[18][19][20][21][22][23] EBV-positive BLderived cell lines have recently been shown to express a broad repertoire of CSPGs. 24 However, the functional significance of CSPG expression in BL is still largely unknown.…”