Increased expression of extracellular matrix metalloproteinase inducer (CD147) in multiple myeloma: Role in regulation of myeloma cell proliferation

B. K. Arendt, D. K. Walters, X. Wu, R. C. Tschumper, P. M. Huddleston, K. J. Henderson, A. Dispenzieri, D. F. Jelinek

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Multiple myeloma (MM) is preceded by the asymptomatic pre-malignant state, monoclonal gammopathy of undetermined significance (MGUS). Although MGUS patients may remain stable for years, they are at increased risk of progressing to MM. A better understanding of the relevant molecular changes underlying the transition from an asymptomatic to symptomatic disease state is urgently needed. Our studies show for the first time that the CD147 molecule (extracellular matrix metalloproteinase inducer) may be having an important biological role in MM. We first demonstrate that CD147 is overexpressed in MM plasma cells (PCs) vs normal and pre-malignant PCs. Next, functional studies revealed that the natural CD147 ligand, cyclophilin B, stimulates MM cell growth. Moreover, when MM patient PCs displaying bimodal CD147 expression were separated into CD147bright and CD147dim populations and analyzed for proliferation potential, we discovered that CD147bright PCs displayed significantly higher levels of cell proliferation than did CD147dim PCs. Lastly, CD147-silencing significantly attenuated MM cell proliferation. Taken together, these data suggest that the CD147 molecule has a key role in MM cell proliferation and may serve as an attractive target for reducing the proliferative compartment of this disease.

Original languageEnglish (US)
Pages (from-to)2286-2296
Number of pages11
JournalLeukemia
Volume26
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • CD147
  • Cyclophilin B
  • Multiple myeloma
  • Plasma cells

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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