title: Toll-like receptors mediate proliferation and survival of multiple myeloma cells.
abstract: Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in bone marrow (BM) and recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections and today 10 human TLRs (TLR1-TLR10) and one TLR-homolog (RP105) have been characterized. B cells express several TLRs (mainly TLR1, 6, 7, 9, 10 and RP105) and TLR-initiated responses in B cells include proliferation, anti-apoptosis effect and plasma cell (PC) differentiation. The present study was designed to analyze the role of TLRs in MM. We show that frequent expressions of TLRs were detected in cell lines from MM patients (minimum six TLRs in each). In comparison, only few TLRs (mainly TLR1 and or RP105) were found expressed in PCs from BM of healthy donors. In addition, TLR-specific ligands induce increased proliferation and survival of the MM cell lines, partially due to an autocrine interleukin-6 production. Importantly, we demonstrate that also PC from MM patients proliferates in response to TLR-specific ligands. In conclusion, TLR-ligands may contribute to increased growth and survival of MM cells in MM patients.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. janne.bohnhorst@ntnu.no
authors.forename: J
authors.initials: J
authors.lastname: Bohnhorst
authors.forename: T
authors.initials: T
authors.lastname: Rasmussen
authors.forename: S H
authors.initials: SH
authors.lastname: Moen
authors.forename: M
authors.initials: M
authors.lastname: Fløttum
authors.forename: L
authors.initials: L
authors.lastname: Knudsen
authors.forename: M
authors.initials: M
authors.lastname: Børset
authors.forename: T
authors.initials: T
authors.lastname: Espevik
authors.forename: A
authors.initials: A
authors.lastname: Sundan
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004151:Dipeptides / Q000494:pharmacology; D005408:Flagellin / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000276:immunology; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011509:Proteoglycans / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053667:Syndecans; D051193:Toll-Like Receptors / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D004151:Dipeptides; D005408:Flagellin; D007093:Imidazoles; D015850:Interleukin-6; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011070:Poly I-C; D011509:Proteoglycans; D012333:RNA, Messenger; D053667:Syndecans; D051193:Toll-Like Receptors; D000093242:Interleukin-6 Inhibitors; C408982:CPG-oligonucleotide; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; C047210:2,3-bis-(palmitoyloxy)-2-propyl-N-palmitoyl-cysteinylserine; C106335:macrophage stimulatory lipopeptide 2; C402365:resiquimod