|
|
 Previous Article | Table of Contents | Next Article 
The Development of a Model for the Homing of Multiple Myeloma Cells to Human Bone Marrow
Mitsuyoshi Urashima,
Benjamin P. Chen,
Shirley Chen,
Geraldine S. Pinkus,
Roderick T. Bronson,
Douglas A. Dedera,
Yasutaka Hoshi,
Gerrard Teoh,
Atsushi Ogata,
Steve P. Treon,
Dharminder Chauhan, and
Kenneth C. Anderson
From the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, the Department of Medicine, Brigham and Womens Hospital, and Department of Pathology, Harvard Medical School, Boston, MA; SyStemix Inc, Palo Alto, CA; the Division of Laboratories, School of Veterinary Medicine, Tufts University, Boston, MA; and the Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
Prior in vitro studies have suggested a role of adhesion molecules, bone marrow stromal cells (BMSCs), and cytokines in the regulation of human multiple myeloma (MM) cell growth and survival. Although in vivo models have been developed in severe combined immunodeficient (SCID) mice that support the growth of human MM within the murine BM microenvironment, these xenograft models do not permit a study of the role of adhesion proteins in human MM cell-human BMSC interactions. We therefore established an in vivo model of human MM using SCID mice implanted with bilateral human fetal bone grafts (SCID-hu mice). For the initial tumor innoculum, human MM derived cell lines (1 × 104 or 5 × 104 ARH-77, OCI-My5, U-266, or RPMI-8226 cells) were injected directly into the BM cavity of the left bone implants in irradiated SCID-hu mice. MM cells engrafted and proliferated in the left human fetal bone implants within SCID-hu mice as early as 4 weeks after injection of as few as 1 × 104 MM cells. To determine whether homing of tumor cells occurred, animals were observed for up to 12 weeks after injection and killed to examine for tumor in the right bone implants. Of great interest, metastases to the right bone implants were observed at 12 weeks after the injection of 5 × 104 MM cells, without spread of human MM cells to murine BM. Human MM cells were identified on the basis of characteristic histology and monoclonal human Ig. Importantly, monoclonal human Ig and human interleukin-6 (IL-6), but not human IL-1 or tumor necrosis factor- , were detectable in sera of SCID-hu mice injected with MM cells. In addition, specific monoclonal Ig light chain deposition was evident within renal tubules. This in vivo model of human MM provides for the first time a means for identifying adhesion molecules that are responsible for specific homing of human MM cells to the human, as opposed to murine, BM microenvironment. Moreover, induction of human IL-6 suggests the possibility that regulation of MM cell growth by this cytokine might also be investigated using this in vivo model.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 754-765
© 1997 by The American Society of Hematology.
 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]
|
|
|
|
|
|
|
H. Rozemuller, E. van der Spek, L. H. Bogers-Boer, M. C. Zwart, V. Verweij, M. Emmelot, R. W. Groen, R. Spaapen, A. C. Bloem, H. M. Lokhorst, et al.
A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect
Haematologica,
July 1, 2008;
93(7):
1049 - 1057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, P. Lin, Y. Shi, J. Romaguera, L. W. Kwak, et al.
A Severe Combined Immunodeficient-hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma
Clin. Cancer Res.,
April 1, 2008;
14(7):
2154 - 2160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Neri, S. Kumar, M. T. Fulciniti, S. Vallet, S. Chhetri, S. Mukherjee, Y. Tai, D. Chauhan, P. Tassone, S. Venuta, et al.
Neutralizing B-Cell Activating Factor Antibody Improves Survival and Inhibits Osteoclastogenesis in a Severe Combined Immunodeficient Human Multiple Myeloma Model
Clin. Cancer Res.,
October 1, 2007;
13(19):
5903 - 5909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Ng, G. Helguera, T. R. Daniels, S. Z. Lomas, J. A. Rodriguez, G. Schiller, B. Bonavida, S. L. Morrison, and M. L. Penichet
Molecular events contributing to cell death in malignant human hematopoietic cells elicited by an IgG3-avidin fusion protein targeting the transferrin receptor
Blood,
October 15, 2006;
108(8):
2745 - 2754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, P. Neri, P. Tassone, H. Yasui, K. Ishitsuka, N. Raje, D. Chauhan, K. Podar, C. Mitsiades, L. Dang, et al.
MLN120B, a Novel I{kappa}B Kinase {beta} Inhibitor, Blocks Multiple Myeloma Cell Growth In vitro and In vivo.
Clin. Cancer Res.,
October 1, 2006;
12(19):
5887 - 5894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Chauhan, G. Li, K. Podar, T. Hideshima, P. Neri, D. He, N. Mitsiades, P. Richardson, Y. Chang, J. Schindler, et al.
A Novel Carbohydrate-Based Therapeutic GCS-100 Overcomes Bortezomib Resistance and Enhances Dexamethasone-Induced Apoptosis in Multiple Myeloma Cells
Cancer Res.,
September 15, 2005;
65(18):
8350 - 8358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, P. Neri, J. L. Kutok, O. Tournilhac, D. D. Santos, E. Hatjiharissi, V. Munshi, S. Venuta, K. C. Anderson, S. P. Treon, et al.
A SCID-hu in vivo model of human Waldenstrom macroglobulinemia
Blood,
August 15, 2005;
106(4):
1341 - 1345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, P. Neri, D. R. Carrasco, R. Burger, V. S. Goldmacher, R. Fram, V. Munshi, M. A. Shammas, L. Catley, G. S. Jacob, et al.
A clinically relevant SCID-hu in vivo model of human multiple myeloma
Blood,
July 15, 2005;
106(2):
713 - 716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Zhu, E. Gerbino, D. M. Beaupre, P. A. Mackley, C. Muro-Cacho, C. Beam, A. D. Hamilton, M. G. Lichtenheld, W. G. Kerr, W. Dalton, et al.
Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells
Blood,
June 15, 2005;
105(12):
4759 - 4766.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, P. Neri, R. Burger, R. Savino, M. Shammas, L. Catley, K. Podar, D. Chauhan, S. Masciari, A. Gozzini, et al.
Combination Therapy with Interleukin-6 Receptor Superantagonist Sant7 and Dexamethasone Induces Antitumor Effects in a Novel SCID-hu In vivo Model of Human Multiple Myeloma
Clin. Cancer Res.,
June 1, 2005;
11(11):
4251 - 4258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Tassone, V. S. Goldmacher, P. Neri, A. Gozzini, M. A. Shammas, K. R. Whiteman, L. L. Hylander-Gans, D. R. Carrasco, T. Hideshima, R. Shringarpure, et al.
Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells
Blood,
December 1, 2004;
104(12):
3688 - 3696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson
Advances in biology of multiple myeloma: clinical applications
Blood,
August 1, 2004;
104(3):
607 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Johrer, K. Janke, J. Krugmann, M. Fiegl, and R. Greil
Transendothelial Migration of Myeloma Cells Is Increased by Tumor Necrosis Factor (TNF)-{alpha} via TNF Receptor 2 and Autocrine Up-Regulation of MCP-1
Clin. Cancer Res.,
March 15, 2004;
10(6):
1901 - 1910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Huang, H.-F. Tien, F.-H. Su, and S.-M. Hsu
Nonirradiated NOD/SCID-Human Chimeric Animal Model for Primary Human Multiple Myeloma: A Potential in Vivo Culture System
Am. J. Pathol.,
February 1, 2004;
164(2):
747 - 756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Harousseau, J. Shaughnessy Jr., and P. Richardson
Multiple Myeloma
Hematology,
January 1, 2004;
2004(1):
237 - 256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Mitsiades, N. S. Mitsiades, R. T. Bronson, D. Chauhan, N. Munshi, S. P. Treon, C. A. Maxwell, L. Pilarski, T. Hideshima, R. M. Hoffman, et al.
Fluorescence Imaging of Multiple Myeloma Cells in a Clinically Relevant SCID/NOD in Vivo Model: Biologic and Clinical Implications
Cancer Res.,
October 15, 2003;
63(20):
6689 - 6696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Richardson, R. L. Schlossman, E. Weller, T. Hideshima, C. Mitsiades, F. Davies, R. LeBlanc, L. P. Catley, D. Doss, K. Kelly, et al.
Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma
Blood,
October 16, 2002;
100(9):
3063 - 3067.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Akiyama, T. Hideshima, T. Hayashi, Y.-T. Tai, C. S. Mitsiades, N. Mitsiades, D. Chauhan, P. Richardson, N. C. Munshi, and K. C. Anderson
Cytokines Modulate Telomerase Activity in a Human Multiple Myeloma Cell Line
Cancer Res.,
July 1, 2002;
62(13):
3876 - 3882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yang, S. Yaccoby, W. Liu, J. K. Langford, C. Y. Pumphrey, A. Theus, J. Epstein, and R. D. Sanderson
Soluble syndecan-1 promotes growth of myeloma tumors in vivo
Blood,
June 28, 2002;
100(2):
610 - 617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Greenstein, K. Ghias, N. L. Krett, and S. T. Rosen
Mechanisms of Glucocorticoid-mediated Apoptosis in Hematological Malignancies
Clin. Cancer Res.,
June 1, 2002;
8(6):
1681 - 1694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Slack, S. Waxman, G. Tricot, M. S. Tallman, and C. D. Bloomfield
Advances in the Management of Acute Promyelocytic Leukemia and Other Hematologic Malignancies with Arsenic Trioxide
Oncologist,
April 1, 2002;
7(90001):
1 - 13.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. Anderson, J. D. Shaughnessy Jr., B. Barlogie, J.-L. Harousseau, and G. D. Roodman
Multiple Myeloma
Hematology,
January 1, 2002;
2002(1):
214 - 240.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K.-W. Peng, G. J. Ahmann, L. Pham, P. R. Greipp, R. Cattaneo, and S. J. Russell
Systemic therapy of myeloma xenografts by an attenuated measles virus
Blood,
October 1, 2001;
98(7):
2002 - 2007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C AUW-HAEDRICH, A SCHMITT-GRAFF, and H WITSCHEL
Isolated episcleral plasmacytoma mimicking episcleritis in a patient with benign monoclonal gammopathy
Br. J. Ophthalmol.,
October 1, 2001;
85(10):
1260d - 1260.
[Full Text]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
F. E. Davies, N. Raje, T. Hideshima, S. Lentzsch, G. Young, Y.-T. Tai, B. Lin, K. Podar, D. Gupta, D. Chauhan, et al.
Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma
Blood,
July 1, 2001;
98(1):
210 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Michigami, N. Shimizu, P. J. Williams, M. Niewolna, S. L. Dallas, G. R. Mundy, and T. Yoneda
Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha 4beta 1-integrin enhances production of osteoclast-stimulating activity
Blood,
September 1, 2000;
96(5):
1953 - 1960.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Dankbar, T. Padro, R. Leo, B. Feldmann, M. Kropff, R. M. Mesters, H. Serve, W. E. Berdel, and J. Kienast
Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma
Blood,
April 15, 2000;
95(8):
2630 - 2636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Urashima, H. Suzuki, Y. Yuza, M. Akiyama, N. Ohno, and Y. Eto
An oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium
Blood,
February 15, 2000;
95(4):
1258 - 1263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Pilarski, G. Hipperson, K. Seeberger, E. Pruski, R. W. Coupland, and A. R. Belch
Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and self-renewal of primary human myeloma in the bone marrow of NOD SCID mice
Blood,
February 1, 2000;
95(3):
1056 - 1065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yaccoby, B. Barlogie, and J. Epstein
Primary Myeloma Cells Growing in SCID-hu Mice: A Model for Studying the Biology and Treatment of Myeloma and Its Manifestations
Blood,
October 15, 1998;
92(8):
2908 - 2913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rebouissou, J. Wijdenes, P. Autissier, K. Tarte, V. Costes, J. Liautard, J.-F. Rossi, J. Brochier, and B. Klein
A gp130 Interleukin-6 Transducer-Dependent SCID Model of Human Multiple Myeloma
Blood,
June 15, 1998;
91(12):
4727 - 4737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Greiner, R. A. Hesselton, and L. D. Shultz
SCID Mouse Models of Human Stem Cell Engraftment
Stem Cells,
May 1, 1998;
16(3):
166 - 177.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Hallek, P. Leif Bergsagel, and K. C. Anderson
Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process
Blood,
January 1, 1998;
91(1):
3 - 21.
[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]
|
|
|
|
|
