|
|
Previous Article | Table of Contents | Next Article 
Blood, 1 October 2000, Vol. 96, No. 7, pp. 2528-2536
NEOPLASIA
Syndecan-1 is targeted to the uropods of polarized myeloma cells
where it promotes adhesion and sequesters heparin-binding
proteins
Magne Børset,
Øyvind Hjertner,
Shmuel Yaccoby,
Joshua Epstein, and
Ralph D. Sanderson
From Arkansas Cancer Research Center and Departments of
Pathology and Anatomy, University of Arkansas for Medical Sciences,
Little Rock, AR; and Institute of Cancer Research and Molecular
Biology, Norwegian University of Science and Technology, Trondheim,
Norway.
Syndecan-1 (CD138) is a heparan sulfate-bearing proteoglycan
present on the surface of myeloma cells where it mediates myeloma cell-cell and cell-extracellular matrix adhesion. In this study, we
examined myeloma cell lines for cell membrane localization of
syndecan-1. On some cells we note a striking localization of syndecan-1
to a single small membrane protrusion, with the remainder of the cell
surface being mostly negative for syndecan-1. Examination of cell
morphology reveals that a proportion of cells from myeloma cell lines,
as well as primary myeloma cells, are polarized, with a uropod on one
end and lamellipodia on the other end. On these polarized cells,
syndecan-1 is specifically targeted to the uropod, but in contrast, on
nonpolarized cells syndecan-1 is evenly distributed over the entire
cell surface. In addition to syndecan-1, several other cell surface
molecules localize specifically to the uropod, including CD44 and CD54.
Functional assays reveal that myeloma cell lines with a high proportion
of polarized cells have a much higher migratory potential than cell
lines with few polarized cells. Moreover, the uropod is the cell pole
preferentially involved in aggregation of myeloma cells and in adhesion
of myeloma cells to osteoblast-like cells. When polarized myeloma cells
are incubated with heparin-binding proteins, like hepatocyte growth
factor or osteoprotegerin, they concentrate in the uropod. These data
indicate that syndecan-1 is targeted to the uropod of polarized myeloma cells and that this targeting plays a role in promoting cell-cell adhesion and may also regulate the biological activity of
heparin-binding cytokines.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
H. Ikeda, T. Hideshima, M. Fulciniti, R. J. Lutz, H. Yasui, Y. Okawa, T. Kiziltepe, S. Vallet, S. Pozzi, L. Santo, et al.
The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells In vitro and In vivo
Clin. Cancer Res.,
June 15, 2009;
15(12):
4028 - 4037.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Lamoureux, G. Picarda, L. Garrigue-Antar, M. Baud'huin, V. Trichet, A. Vidal, E. Miot-Noirault, B. Pitard, D. Heymann, and F. Redini
Glycosaminoglycans as Potential Regulators of Osteoprotegerin Therapeutic Activity in Osteosarcoma
Cancer Res.,
January 15, 2009;
69(2):
526 - 536.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Purushothaman, L. Chen, Y. Yang, and R. D. Sanderson
Heparanase Stimulation of Protease Expression Implicates It as a Master Regulator of the Aggressive Tumor Phenotype in Myeloma
J. Biol. Chem.,
November 21, 2008;
283(47):
32628 - 32636.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y.-T. Tai, M. Dillon, W. Song, M. Leiba, X.-F. Li, P. Burger, A. I. Lee, K. Podar, T. Hideshima, A. G. Rice, et al.
Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu
Blood,
August 15, 2008;
112(4):
1329 - 1337.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yang, V. MacLeod, Y. Dai, Y. Khotskaya-Sample, Z. Shriver, G. Venkataraman, R. Sasisekharan, A. Naggi, G. Torri, B. Casu, et al.
The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy
Blood,
September 15, 2007;
110(6):
2041 - 2048.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yang, V. MacLeod, H.-Q. Miao, A. Theus, F. Zhan, J. D. Shaughnessy Jr., J. Sawyer, J.-P. Li, E. Zcharia, I. Vlodavsky, et al.
Heparanase Enhances Syndecan-1 Shedding: A NOVEL MECHANISM FOR STIMULATION OF TUMOR GROWTH AND METASTASIS
J. Biol. Chem.,
May 4, 2007;
282(18):
13326 - 13333.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Pearse
Wnt antagonism in multiple myeloma: a potential cause of uncoupled bone remodeling.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6274s - 6278s.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Nadav, B.-Z. Katz, S. Baron, N. Cohen, E. Naparstek, and B. Geiger
The Generation and Regulation of Functional Diversity of Malignant Plasma Cells.
Cancer Res.,
September 1, 2006;
66(17):
8608 - 8616.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Dai, Y. Yang, V. MacLeod, X. Yue, A. C. Rapraeger, Z. Shriver, G. Venkataraman, R. Sasisekharan, and R. D. Sanderson
HSulf-1 and HSulf-2 Are Potent Inhibitors of Myeloma Tumor Growth in Vivo
J. Biol. Chem.,
December 2, 2005;
280(48):
40066 - 40073.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Kelly, L. J. Suva, Y. Huang, V. MacLeod, H.-Q. Miao, R. C. Walker, and R. D. Sanderson
Expression of Heparanase by Primary Breast Tumors Promotes Bone Resorption in the Absence of Detectable Bone Metastases
Cancer Res.,
July 1, 2005;
65(13):
5778 - 5784.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. A. Mosheimer, N. C. Kaneider, C. Feistritzer, A. M. Djanani, D. H. Sturn, J. R. Patsch, and C. J. Wiedermann
Syndecan-1 Is Involved in Osteoprotegerin-Induced Chemotaxis in Human Peripheral Blood Monocytes
J. Clin. Endocrinol. Metab.,
May 1, 2005;
90(5):
2964 - 2971.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Vincent, D. K. Jin, M. A. Karajannis, K. Shido, A. T. Hooper, W. K. Rashbaum, B. Pytowski, Y. Wu, D. J. Hicklin, Z. Zhu, et al.
Fetal Stromal-Dependent Paracrine and Intracrine Vascular Endothelial Growth Factor-A/Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Proliferation and Motility of Human Primary Myeloma Cells
Cancer Res.,
April 15, 2005;
65(8):
3185 - 3192.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Tkachenko, J. M. Rhodes, and M. Simons
Syndecans: New Kids on the Signaling Block
Circ. Res.,
March 18, 2005;
96(5):
488 - 500.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. K. Langford, Y. Yang, T. Kieber-Emmons, and R. D. Sanderson
Identification of an Invasion Regulatory Domain within the Core Protein of Syndecan-1
J. Biol. Chem.,
February 4, 2005;
280(5):
3467 - 3473.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yang, V. MacLeod, M. Bendre, Y. Huang, A. M. Theus, H.-Q. Miao, P. Kussie, S. Yaccoby, J. Epstein, L. J. Suva, et al.
Heparanase promotes the spontaneous metastasis of myeloma cells to bone
Blood,
February 1, 2005;
105(3):
1303 - 1309.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Hov, R. U. Holt, T. B. Ro, U.-M. Fagerli, H. Hjorth-Hansen, V. Baykov, J. G. Christensen, A. Waage, A. Sundan, and M. Borset
A Selective c-Met Inhibitor Blocks an Autocrine Hepatocyte Growth Factor Growth Loop in ANBL-6 Cells and Prevents Migration and Adhesion of Myeloma Cells
Clin. Cancer Res.,
October 1, 2004;
10(19):
6686 - 6694.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Podar, L. P. Catley, Y.-T. Tai, R. Shringarpure, P. Carvalho, T. Hayashi, R. Burger, R. L. Schlossman, P. G. Richardson, L. N. Pandite, et al.
GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment
Blood,
May 1, 2004;
103(9):
3474 - 3479.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. C. Frasch, P. M. Henson, K. Nagaosa, M. B. Fessler, N. Borregaard, and D. L. Bratton
Phospholipid Flip-Flop and Phospholipid Scramblase 1 (PLSCR1) Co-localize to Uropod Rafts in Formylated Met-Leu-Phe-stimulated Neutrophils
J. Biol. Chem.,
April 23, 2004;
279(17):
17625 - 17633.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Okuma, K. P. Dalton, L. Buonocore, E. Ramsburg, and J. K. Rose
Development of a Novel Surrogate Virus for Human T-Cell Leukemia Virus Type 1: Inhibition of Infection by Osteoprotegerin
J. Virol.,
August 1, 2003;
77(15):
8562 - 8569.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yang, M. Borset, J. K. Langford, and R. D. Sanderson
Heparan Sulfate Regulates Targeting of Syndecan-1 to a Functional Domain on the Cell Surface
J. Biol. Chem.,
April 4, 2003;
278(15):
12888 - 12893.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Standal, C. Seidel, O. Hjertner, T. Plesner, R. D. Sanderson, A. Waage, M. Borset, and A. Sundan
Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells
Blood,
September 26, 2002;
100(8):
3002 - 3007.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Y. Pumphrey, A. M. Theus, S. Li, R. S. Parrish, and R. D. Sanderson
Neoglycans, Carbodiimide-modified Glycosaminoglycans: A New Class of Anticancer Agents That Inhibit Cancer Cell Proliferation and Induce Apoptosis
Cancer Res.,
July 1, 2002;
62(13):
3722 - 3728.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Dominguez-Jimenez, D. Sancho, M. Nieto, M. C. Montoya, O. Barreiro, F. Sanchez-Madrid, and R. Gonzalez-Amaro
Effect of pentoxifylline on polarization and migration of human leukocytes
J. Leukoc. Biol.,
April 1, 2002;
71(4):
588 - 596.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. W. B. Derksen, R. M. J. Keehnen, L. M. Evers, M. H. J. van Oers, M. Spaargaren, and S. T. Pals
Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma
Blood,
February 15, 2002;
99(4):
1405 - 1410.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Millan, M. C. Montoya, D. Sancho, F. Sanchez-Madrid, and M. A. Alonso
Lipid rafts mediate biosynthetic transport to the T lymphocyte uropod subdomain and are necessary for uropod integrity and function
Blood,
February 1, 2002;
99(3):
978 - 984.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Chen, B. Gong, A. S. Mahmoud-Ahmed, A. Zhou, E. D. Hsi, M. Hussein, and A. Almasan
Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma
Blood,
October 1, 2001;
98(7):
2183 - 2192.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Seidel, O. Hjertner, N. Abildgaard, L. Heickendorff, M. Hjorth, J. Westin, J. L. Nielsen, H. Hjorth-Hansen, A. Waage, A. Sundan, et al.
Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease
Blood,
October 1, 2001;
98(7):
2269 - 2271.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Pearse, E. M. Sordillo, S. Yaccoby, B. R. Wong, D. F. Liau, N. Colman, J. Michaeli, J. Epstein, and Y. Choi
Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression
PNAS,
September 13, 2001;
(2001)
201394498.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Pearse, E. M. Sordillo, S. Yaccoby, B. R. Wong, D. F. Liau, N. Colman, J. Michaeli, J. Epstein, and Y. Choi
Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression
PNAS,
September 25, 2001;
98(20):
11581 - 11586.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|