Am J Blood Res 2013;3(4):271-285
Original Article
N-cadherin impedes proliferation of the multiple myeloma cancer stem cells
Nicole M Sadler, Britney R Harris, Brittany A Metzger, Julia Kirshner
Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA
Received October 10, 2013; Accepted December 6, 2013; Epub December 18, 2013; Published December 30, 2013
Abstract: Multiple myeloma (MM) is an incurable malignancy of the plasma cells localized to the bone marrow. A rare
population of MM cancer stem cells (MM-CSCs) has been shown to be responsible for maintaining the pull of residual
disease and to contribute to myeloma relapse. The stem cells are found in a bone marrow niche in contact with the stromal
cells that are responsible for maintaining the proliferative quiescence of the MM-CSC and regulate its self-renewal and
differentiation decisions. Here we show that both MM and bone marrow stromal cells express N-cadherin, a cell-cell adhesion
molecule shown to maintain a pool of leukemic stem cells. Inhibition of N-cadherin using a neutralizing antibody led to an
increase in the MM cell proliferation. A decrease in MM cell adhesion to the bone marrow stroma was observed in the first 24
hours of co-culture followed by a 2.3-30-fold expansion of the adherent cells. Moreover, inhibition of N-cadherin led to a 4.8-9.6-
fold expansion of the MM-CSC population. Surprisingly, addition of the N-cadherin antagonist peptide resulted in massive
death of the non-adherent MM cells, while the viability of the adherent cells and MM-CSCs remained unaffected. Interestingly,
the proliferative effects of N-cadherin inhibition were not mediated by the nuclear translocation of β-catenin. Taken together,
our findings demonstrate the crucial role of N-cadherin in regulating MM cell proliferation and viability and open an interesting
avenue of investigation to understand how structural modifications of N-cadherin can affect MM cell behavior. Our findings
suggest that targeting N-cadherin may be a useful therapeutic strategy to treat MM in conjunction with an agent that has anti-
MM-CSC activity. (AJBR1310001).
Keywords: Multiple myeloma, cancer stem cells, N-cadherin
Address correspondence to: Julia Kirshner, Department of Biological Sciences, Purdue University, 201 S. University Street,
West Lafayette, IN 47907, USA. Tel: 765-494-2843; Fax: 765-496-1496; E-mail: jkirshne@purdue.edu
Original Article
N-cadherin impedes proliferation of the multiple myeloma cancer stem cells
Nicole M Sadler, Britney R Harris, Brittany A Metzger, Julia Kirshner
Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA
Received October 10, 2013; Accepted December 6, 2013; Epub December 18, 2013; Published December 30, 2013
Abstract: Multiple myeloma (MM) is an incurable malignancy of the plasma cells localized to the bone marrow. A rare
population of MM cancer stem cells (MM-CSCs) has been shown to be responsible for maintaining the pull of residual
disease and to contribute to myeloma relapse. The stem cells are found in a bone marrow niche in contact with the stromal
cells that are responsible for maintaining the proliferative quiescence of the MM-CSC and regulate its self-renewal and
differentiation decisions. Here we show that both MM and bone marrow stromal cells express N-cadherin, a cell-cell adhesion
molecule shown to maintain a pool of leukemic stem cells. Inhibition of N-cadherin using a neutralizing antibody led to an
increase in the MM cell proliferation. A decrease in MM cell adhesion to the bone marrow stroma was observed in the first 24
hours of co-culture followed by a 2.3-30-fold expansion of the adherent cells. Moreover, inhibition of N-cadherin led to a 4.8-9.6-
fold expansion of the MM-CSC population. Surprisingly, addition of the N-cadherin antagonist peptide resulted in massive
death of the non-adherent MM cells, while the viability of the adherent cells and MM-CSCs remained unaffected. Interestingly,
the proliferative effects of N-cadherin inhibition were not mediated by the nuclear translocation of β-catenin. Taken together,
our findings demonstrate the crucial role of N-cadherin in regulating MM cell proliferation and viability and open an interesting
avenue of investigation to understand how structural modifications of N-cadherin can affect MM cell behavior. Our findings
suggest that targeting N-cadherin may be a useful therapeutic strategy to treat MM in conjunction with an agent that has anti-
MM-CSC activity. (AJBR1310001).
Keywords: Multiple myeloma, cancer stem cells, N-cadherin
Address correspondence to: Julia Kirshner, Department of Biological Sciences, Purdue University, 201 S. University Street,
West Lafayette, IN 47907, USA. Tel: 765-494-2843; Fax: 765-496-1496; E-mail: jkirshne@purdue.edu
| AJBR Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |
 |  |  |  |  |  |  |