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: Unn-Merete Fagerli, Randi U Holt, Toril Holien, Thea K Vaatsveen, Fenghuang Zhan, Kjartan W Egeberg, Bart Barlogie, Anders Waage, Harald Aarset, Hong Yan Dai, John D Shaughnessy Jr, Anders Sundan, Magne Børset
• Journal: Blood (Blood) Vol. 111 Issue 2 Pg. 806-15 (Jan 15 2008) ISSN: 0006-4971 [Print] United States
• PMID: 17934070 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Neoplasm Proteins
• RNA, Messenger
• RNA, Neoplasm
• PTP4A3 protein, human
• Protein Tyrosine Phosphatases

Topics

• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cytokines (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Silencing
• Humans
• Male
• Multiple Myeloma (metabolism, pathology)
• Neoplasm Metastasis
• Neoplasm Proteins (antagonists & inhibitors, biosynthesis, genetics)
• Plasma Cells (metabolism, pathology)
• Protein Tyrosine Phosphatases (antagonists & inhibitors, biosynthesis, genetics)
• RNA, Messenger (biosynthesis, genetics)
• RNA, Neoplasm (biosynthesis, genetics)
• Randomized Controlled Trials as Topic