title: Metallothionein-I + II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas.
abstract: Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is highly malignant and has a poor prognosis. The PCNSL molecular features are reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL shows unique molecular profiles and a distinct clinical behavior. This article characterizes the histopathology and expression profiles of metallothionein-I + II (MT-I + II) and their receptor megalin along with proliferation, oxidative stress, and apoptosis in PCNSL and in central nervous system (CNS) lymphomas due to relapse from DLBCL (collectively referred to as CNS lymphoma). We show for the first time that MT-I + II and megalin are significantly altered in CNS lymphoma relative to controls (reactive lymph nodes and non-lymphoma brain tissue with neuropathology). MT-I + II are secreted in the CNS and are found mainly in the lymphomatous cells, while their receptor megalin is increased in cerebral cells. This morphology likely reflects the CNS lymphoma microenvironment and molecular interactions between lymphomatous and neuronal cells.
authors.affiliation: Section of Neuroprotection, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark. M.PENKOWA@sund.ku.dk
authors.forename: Mie Ø
authors.initials: MØ
authors.lastname: Pedersen
authors.forename: Per B
authors.initials: PB
authors.lastname: Hansen
authors.forename: Signe L
authors.initials: SL
authors.lastname: Nielsen
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000032:analysis; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000032:analysis*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008315:Malondialdehyde / Q000032:analysis; D008668:Metallothionein / Q000032:analysis*; D008875:Middle Aged; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000032:analysis; D018384:Oxidative Stress; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D009687:Nuclear Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C024829:8-hydroxyguanine; D006147:Guanine; D008668:Metallothionein; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7