Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.
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.
Fagerli
Unn-Merete
UM
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
Holt
Randi U
RU
Holien
Toril
T
Vaatsveen
Thea K
TK
Zhan
Fenghuang
F
Egeberg
Kjartan W
KW
Barlogie
Bart
B
Waage
Anders
A
Aarset
Harald
H
Dai
Hong Yan
HY
Shaughnessy
John D
JD
Sundan
Anders
A
Børset
Magne
M
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
D016207:Cytokines; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases