Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 2, February, p. 153–158

doi: 10.17219/acem/68271

Publication type: original article

Language: English

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Blocking MET receptor signaling in multiple myeloma cells in vitro and in vivo

Artur Jurczyszyn1,A,B,C,D,E,F, Anna Zebzda2,A,B,C,D,E,F, Joanna Gdula-Argasińska3,D,F, Jacek Czepiel4,E,F, David H. Vesole5,6,E,F, William Perucki7,D, Marcin Majka2,A,B,C,D,E,F

1 Department of Hematology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland

2 Department of Transplantology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland

3 Radioligand Department, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland

4 Department of Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland

5 John Theurer Cancer Center, Hackensack University Medical Center, USA

6 School of Medicine, Georgetown University, USA

7 John Dempsey Hospital, Department of Medicine, University of Connecticut, Farmington, USA

Abstract

Background. Numerous studies have shown a role of the hepatocyte growth factor (HGF) as a ligand for the MET receptor in promoting aggressiveness in myeloma cells.
Objectives. The aim of this study was to confirm the presence of the MET receptor in myeloma cell lines, to establish a stable lentiviral construct directed against MET receptor mRNA and then to evaluate the effect of blocking MET receptor expression both in vitro and in vivo.
Material and Methods. The U266 and INA6 cells were transduced using a lentiviral vector carrying siRNA to achieve the reduction of MET receptor expression. The ocular sinus of NOD/SCID mice was injected with wt-U266, shMET-U266 and shLacZ-U266 cells.
Results. MET receptor expression was demonstrated in all tested myeloma cell lines. Blocking the HGF/MET axis did not affect the growth of transduced U266 and INA6 cell lines. The inoculation of NOD/SCID mice with myeloma cells with reduced expression of MET led to increased survival of the animals.
Conclusion. MET receptor expression was constituently expressed in all tested myeloma cell lines. A lentiviral construct can effectively reduce the expression of the MET receptor in myeloma cells. Further studies are necessary to evaluate the effect of the reduction of MET receptor expression in multiple myeloma, focusing on animal models with a larger test group size.

Key words

hepatocyte growth factor, transduction, U266, INA6

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