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Blood, 15 January 2008, Vol. 111, No. 2, pp. 806-815.
Prepublished online as a Blood First Edition Paper on October 12, 2007; DOI 10.1182/blood-2007-07-101139.
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Submitted July 12, 2007
Accepted September 30, 2007
Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells
Unn-Merete Fagerli*, Randi Utne Holt, Toril Holien, Thea Kristin Vaatsveen, Fenghuang Zhan, Kjartan W Egeberg, Bart Barlogie, Anders Waage, Harald Aarset, Hong Yan Dai, John D. Shaughnessy Jr, Anders Sundan, and Magne Borset
Department of Oncology, St. Olavs University Hospital, Trondheim, Norway
Faculty of Technology, Sor-Trondelag University College, Trondheim, Norway
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
Myeloma Institute for Research and Therapy, University Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
Department of Hematology, St. Olavs University Hospital, Trondheim, Norway
Department of Pathology and Molecular Genetics, St. Olavs University Hospital, Trondheim, Norway
Department of Immunology, St. Olavs University Hospital, Trondheim, Norway
* Corresponding author; email: unn-merete.fagerli{at}ntnu.no.
Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of two 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 both at the mRNA and protein level. There was significantly higher expression of the PRL-3 gene in PCs from patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), Smouldering myeloma (SMM) and myeloma than in normal PCs. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significant higher in the 3 groups denoted as Proliferation, Low Bone Disease, and MMSET/FGFR3. PRL-3 protein was detected in 18 out 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.
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