title: Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.
abstract: Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, and Department of Immunology and Transfusion Medicine, St Olavs University Hospital, Trondheim, Norway. unn-merete.fagerli@ntnu.no
authors.forename: Unn-Merete
authors.initials: UM
authors.lastname: Fagerli
authors.forename: Randi U
authors.initials: RU
authors.lastname: Holt
authors.forename: Toril
authors.initials: T
authors.lastname: Holien
authors.forename: Thea K
authors.initials: TK
authors.lastname: Vaatsveen
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Kjartan W
authors.initials: KW
authors.lastname: Egeberg
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.forename: Harald
authors.initials: H
authors.lastname: Aarset
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Dai
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Anders
authors.initials: A
authors.lastname: Sundan
authors.forename: Magne
authors.initials: M
authors.lastname: Børset
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases