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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.
Highlights
Proteoglycans (PGs) are complex macromolecules composed of a core protein and covalently linked polysaccharide chain(s) which play a critical role in cell-cell and cell-matrix interactions
A panel of Epstein-Barr virus (EBV)+ Burkitt’s lymphoma cell lines with different EBV latency stages and lymphoblastoid B cell lines generated by EBV transformation of normal human B cells in vitro (CBMIRal-STO, CBC-JK2-STO, Nad20) were used (Table 1)
Expression of main PGs in the cell lines was studied by real-time RT-PCR analysis (Figure 1, Supplementary Table S1)
Summary
Proteoglycans (PGs) are complex macromolecules composed of a core protein and covalently linked polysaccharide chain(s) which play a critical role in cell-cell and cell-matrix interactions. Disruptions of such interactions might affect B cell interaction with surrounding stroma and may perturb the cell phenotypes. Regulated HSPGs expression is a requirement for normal B cell maturation, differentiation and function [4] and the conformation of their HS polysaccharide chains is crucial for recruitment of factors that control plasma cell survival [5]. Exogenous extracellular heparin inhibits BL cell proliferation while internalized heparin promotes www.impactjournals.com/oncotarget it [7], and treatment of B cells with chondroitin sulphate (CS) activates B cells in vitro and induces HSPG CD138/ syndecan-1 expression, affecting humoral immune response in mice [8]
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