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

TY - JOUR

T1 - Blocking MET receptor signaling in multiple myeloma cells in vitro and in vivo

AU - Jurczyszyn, Artur

AU - Zebzda, Anna

AU - Gdula-Argasinska, Joanna

AU - Czepiel, Jacek

AU - Vesole, David H.

AU - Perucki, William

AU - Majka, Marcin

N1 - Publisher Copyright: © 2018 by Wroclaw Medical University.

PY - 2018/2

Y1 - 2018/2

N2 - 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. Conclusions. 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.

AB - 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. Conclusions. 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.

KW - Hepatocyte growth factor

KW - INA6

KW - Transduction

KW - U266

UR - https://www.scopus.com/pages/publications/85043227395

U2 - 10.17219/acem/68271

DO - 10.17219/acem/68271

M3 - Article

C2 - 29521056

SN - 1899-5276

VL - 27

SP - 153

EP - 158

JO - Advances in Clinical and Experimental Medicine

JF - Advances in Clinical and Experimental Medicine

IS - 2

ER -