Abstract
One of the main characteristics of multiple myeloma cells is their predominant localization in the bone marrow. It is, however, unclear whether this is due to a selective initial entry, or whether this entry is more random and other processes like survival and/or growth stimulation, only present in the medullar microenvironment, are unique. To investigate this, in vivo homing kinetics of murine 5T2MM cells shortly after injection were assessed in bone marrow, liver, spleen, lungs, heart, intestines, kidney and testis by tracing of radiolabelled cells, by immunostaining of isolated cells and by polymerase chain reaction analysis. We demonstrated the presence of 5T2MM cells in bone marrow, spleen and liver with all other organs being negative. Adhesion assays of 5T2MM cells to different types of endothelial cells demonstrated a selective adhesion of 5T2MM cells to bone marrow and liver and not to lung endothelial cells. We here demonstrate that the specific in vivo localization of the 5T2MM cells is a result of the combination of a selective entry/adhesion of the 5T2MM cells in the bone marrow, spleen and liver, and a selective survival and growth of these tumour cells in the bone marrow and spleen but not in the liver. © 2000 Cancer Research Campaign
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References
Aoudjit F, Potworowski EF and St-Pierre Y (1998) The metastatic characteristics of murine lymphoma cell lines in vivo are manifested after target organ invasion. Blood 91: 623–629
Bakkus MH, Heirman C, Van Riet I, Van Camp B and Thielemans K (1992) Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. Blood 80: 2326–2335
Berlin-Rufenach C, Otto F, Mathies M, Westermann J, Owen MJ, Hamann A and Hogg N (1999) Lymphocyte migration in lymphocyte function-associated antigen (LFA-1)-deficient mice. J Exp Med 9: 1467–1478
Bianchi E, Bender JR, Blasi F and Pardi R (1997) Through and beyond the wall: late steps in leukocyte transendothelial migration. Immunol Today 18: 586–591
Blair A and Thomas DB (1997) Preferential adhesion of fetal liver derived primitive haemopoietic progenitor cells to bone marrow stroma. Br J Haematol 99: 726–731
Butcher EC and Picker LJ (1996) Lymphocyte homing and homeostasis. Science 272: 60–66
Cardier JE and Barbera-Guillem E (1997) Extramedullary hematopoiesis in adult liver is associated with specific sinusoidal endothelial cells. Hepatology 26: 165–175
Coligan JE, Kruisbeek AM, Margulies DH, Shevach EM and Strober W (1984) Induction and measurement of cytotoxic T lymphocyte activity. Current Protocols in Immunology, Coico R (ed) pp. 3–11.14, Wiley Interscience:
De Bleser P, Niki T, Rogiers V and Geerts A (1997) Transforming growth factor-β gene expression in normal and fibrotic rat liver. J Hepatol 26: 886–893
Feng D, Nagy JA, Pyne K, Dvorak HF and Dvorak AM (1998) Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 187: 903–915
Frenette PS, Subbarao S, Mazo IB, von Adrian UH and Wagner DD (1998) Endothelial selectins and vascular cell adhesion molecule-1 promote hematopietic progenitor homing to bone marrow. Proc Natl Acad Sci USA 95: 14423–14428
Hallek M, Bergsagel PL and Anderson KC (1998) Multiple myeloma: increasing evidence for a multistep transformation process. Blood 91: 3–31
Hardin J, MacLeod S, Grigorieva I, Chang R, Barlogie B, Xiao H and Epstein J (1994) Interleukin-6 prevents dexamathasone-induced myeloma cell death. Blood 84: 3063–3070
Imai K and Kobayashi M (1998) Differences between bone marrow and lung endothelial cells. Semin Thromb Hemostas 24: 275–277
Imai K, Kobayashi M, Wang J, Ohiro Y, Hamada JI, Cho Y, Imamura M, Musashi M, Kondo T, Hosokawa M and Asaka M (1999) Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells. Blood 93: 149–156
Jaeschke H and Smith CW (1997) Cell adhesion and migration. III. Leukocyte adhesion and transmigration in the liver vasculature. Am J Physiol 273, Gastrointest. Liver Physiol G1169–1173
Jonas P, Holzmann B, Jablonski-Westrich D and Hamann A (1998) Dissemination capacity of murine lymphoma cells is not dependent on efficient homing. Int J Cancer 77: 402–407
Juge-Morineau N, Francois S, Puthier D, Godard A, Bataille R and Amiot M (1995) The gp130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells. Br J Haematol 90: 707–710
Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A and Kishimoto T (1988) Autocrine generation and requirement of BSF-2/I1-6 for human multiple myelomas. Nature 332: 83–85
Klein B, Zhang XG, Jourdan M, Content J, Houssiu F, Aarden L, Piechaczyk M and Bataille R (1989) Paracrine rather than autocrine regulation of myeloma-cell growth and differentation by interleukin-6. Blood 73: 517–526
Mazo IB, Gutierrez-Ramos JC, Frenette PS, Hynes RO, Wagner DD and von Andrian UH (1998) Hematopoietic progenitor cell rolling in BM microvessels: parallel contributions by endothelial selectins and vascular adhesion molecule 1. J Exp Med 188: 465–474
Pope B, Brown R, Gibson J and Joshua D (1997) Plasma cells in peripheral blood stem cell harvest from patients with multiple myeloma are predominantly polyclonal. Bone Marrow Transplant 20: 205–210
Radl J, De Glopper E, Schuit HRE and Zurcher C (1979) Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice. J Immunol 122: 609–613
Salmi M, Adams D and Jalkanen S (1998) Cell adhesion and migration. IV. Lymphocyte trafficking in the intestine and liver. Am J Physiol 274, Gastrointest. Liver Physiol G1–G6
Smedsrod B and Pertoft H (1985) Preparation of pure hepatocytes and reticuloendothelial cells in high yield from a single rat liver by means of Percoll centrifugation and selective adherence. J Leukoc Biol 38: 213–230
Smith ME and Ford WL (1983) The recirculating lymphocyte pool of the rat: a systematic description of the migratory behaviour of recirculating lymphocytes. Immunology 49: 83–94
Tanigushi H, Toyoshima T, Fukao K and Nakauchi H (1996) Presence of hematopoietic stem cells in the adult liver. Nat Med 2: 198–203
Tietz W and Hamann A (1997) The migratory behaviour of murine CD4+ cells of memory phenotype. Eur J Immunol 27: 2225–2232
Uchiyama H, Barut KA, Mohrabacher AF, Chauchan D and Anderson KC (1993) Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 seceretion. Blood 82: 3712–3720
Van Riet I, Heirman C, Lacor P, De Waele M, Thielemans K and Van Camp B (1989) Detection of monoclonal B lymphocytes in bone marow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangements studies. Br J Haematol 73: 289–295
Van Riet I, De Greef C, Aharchi F, Woischwill C, De Waele M, Bakkus M, Lacor P, Schots R and Van Camp B (1997) Establishment and characterization of a human stroma-dependent myeloma cell line (MM5.1) and its stroma-independent variant (MM5.2). Leukemia 11: 284–293
Van Riet I, Vanderkerken K, De Greef C and Van Camp, (1998) Homing behaviour of the malignant cell clone in multiple myeloma. Medical Oncology 15: 154–164
Vanderkerken K, Goes E, De Raeve H, Radl J and Van Camp B (1996) Follow-up of bone lesions in an experimental multiple myeloma mouse model: description of an in vivo technique using radiography dedicated for mammography. Br J Cancer 73: 1463–1465
Vanderkerken K, De Raeve H, Goes E, Van Meirvenne S, Radl J, Van Riet I, Thielemans K and Van Camp B (1997) Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse. Br J Cancer 76: 451–460
Vanderkerken K, Asosingh K, Braet F, Van Riet I and Van Camp B (1999) Insulin like growth factor-1 acts as a chemoattractant factor for 5T2 multiple myeloma cells. Blood 93: 235–241
Van Rooijen N (1989) The liposome-mediated ‘suicide’ technique. J Immunol Methods 124: 1–6
Van Rooijen N and Sanders A (1996) Kupffer cell depletion by liposome-delivered drugs: comparative activity by intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid. Hepatology 23: 1239–1243
Zhu D, Van Arkel C, King CA, Van Meirvenne S, De Greef C, Thielemans K, Radl J and Stevenson K (1998) Immunoglobulin VHgene sequence analysis of spontaneous murine immunoglobule-secreting B-cell tumors with clinical features of human disease. Immunology 93: 162–170
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Vanderkerken, K., Greef, C., Asosingh, K. et al. Selective initial in vivo homing pattern of 5T2 multiple myeloma cells in the C57BL/KalwRij mouse. Br J Cancer 82, 953–959 (2000). https://doi.org/10.1054/bjoc.1999.1024
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DOI: https://doi.org/10.1054/bjoc.1999.1024
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