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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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NEOPLASIA

Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells

Unn-Merete Fagerli1,5, Randi U. Holt1,7, Toril Holien1, Thea K. Vaatsveen1, Fenghuang Zhan2, Kjartan W. Egeberg1, Bart Barlogie2, Anders Waage1,6, Harald Aarset4, Hong Yan Dai1,4, John D. Shaughnessy, Jr2, Anders Sundan1, and Magne Børset1,3

1 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; 2 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR; Departments of3 Immunology and Transfusion Medicine 4 Pathology and Molecular Genetics 5 Oncology, and 6 Hematology, St Olavs University Hospital, Trondheim, Norway; and 7 Faculty of Technology, Sør-Trøndelag University College, Trondheim, Norway

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.


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