Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays
10.1182/blood.v98.3.771
Crossref journal-article
American Society of Hematology
Blood (234)
Abstract

AbstractIn multiple myeloma (MM), the growth of primary plasma cells depends not only on interleukin-6 (IL-6), but also on additional unidentified signals delivered by the bone marrow environment. Using Atlas complementary DNA (cDNA) arrays comprising 268 genes coding for intercellular signaling molecules, this study identified genes that are overexpressed in myeloma cells compared to autologous B-lymphoblastoid cell lines. These genes encode the oncogenic Tyro3 tyrosine kinase receptor, the heparin-binding epidermal growth factor–like growth factor (HB-EGF) that is an epithelial autocrine tumor growth factor, the thrombin receptor (TR) that is linked to HB-EGF and syndecan-1 processing and to cell invasion, chemokine receptors CCR1 and CCR2, the Wnt pathway actor Frizzled-related protein (FRZB), and the Notch receptor ligand Jagged 2. These data, obtained with the Atlas cDNA array, were confirmed by reverse transcriptase–polymerase chain reaction or protein analysis or both. Furthermore, Tyro3,HB-EGF, TR, and FRZB gene expression was documented in purified primary malignant plasma cells from patients with plasma cell leukemia or MM. HB-EGF and FRZB were poorly expressed in purified polyclonal plasma cells. Finally, HB-EGF was proved to be an essential autocrine growth factor for the XG-1 myeloma cells. This study shows the potency and the biologic relevance of cDNA arrays used to analyze simultaneously a large panel of intercellular signaling genes and, by identifying several genes overexpressed in malignant plasma cells, opens new fields of investigation in MM biology.

Bibliography

De Vos, J., Couderc, G., Tarte, K., Jourdan, M., Requirand, G., Delteil, M.-C., Rossi, J.-F., Mechti, N., & Klein, B. (2001). Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays. Blood, 98(3), 771–780.

Authors 9
  1. John De Vos (first)
  2. Guilhem Couderc (additional)
  3. Karin Tarte (additional)
  4. Michel Jourdan (additional)
  5. Guilhem Requirand (additional)
  6. Marie-Claude Delteil (additional)
  7. Jean-François Rossi (additional)
  8. Nadir Mechti (additional)
  9. Bernard Klein (additional)
References 75 Referenced 127
  1. 10.1016/S0092-8674(00)81683-9 / Cell. / The hallmarks of cancer. by Hanahan (2000)
  2. {'key': '2020021223254219100_B2', 'first-page': '728', 'article-title': 'Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies.', 'volume': '59', 'author': 'Bellamy', 'year': '1999', 'journal-title': 'Cancer Res.'} / Cancer Res. / Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. by Bellamy (1999)
  3. 10.1182/blood.V93.9.3064 / Blood. / Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. by Vacca (1999)
  4. 10.1182/blood.V95.8.2630 / Blood. / Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. by Dankbar (2000)
  5. 10.1182/blood.V88.8.3101.bloodjournal8883101 / Blood. / Different CD44 splicing patterns define prognostic subgroups in multiple myeloma. by Stauder (1996)
  6. 10.1182/blood.V82.12.3712.3712 / Blood. / Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. by Uchiyama (1993)
  7. 10.1182/blood.V84.7.2269.2269 / Blood. / Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. by Lokhorst (1994)
  8. 10.1182/blood.V73.2.517.517 / Blood. / Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. by Klein (1989)
  9. 10.1046/j.1365-2141.1998.01101.x / Br J Haematol. / Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production. by Costes (1998)
  10. 10.1038/sj.leu.2400873 / Leukemia. / Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma. by Donovan (1998)
  11. 10.1182/blood.V73.8.2145.2145 / Blood. / Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma. by Kawano (1989)
  12. 10.1038/sj.leu.2401632 / Leukemia. / Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors. by Gu (2000)
  13. 10.1073/pnas.90.5.2060 / Proc Natl Acad Sci U S A. / In vitro culture of primary plasmacytomas requires stromal cell feeder layers. by Degrassi (1993)
  14. 10.1046/j.1365-2141.1998.00517.x / Br J Haematol. / Long-term bone marrow cultured stromal cells regulate myeloma tumour growth in vitro: studies with primary tumour cells and LTBMC-dependent cell lines. by Bloem (1998)
  15. 10.1038/sj.leu.2400564 / Leukemia. / Establishment and characterization of a human stroma-dependent myeloma cell line (MM5.1) and its stroma-independent variant (MM5.2). by Van Riet (1997)
  16. 10.1038/ng0797-260 / Nat Genet. / Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. by Chesi (1997)
  17. 10.1182/blood.V95.3.992.003k29_992_998 / Blood. / Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cell proliferation and prevents apoptosis. by Plowright (2000)
  18. 10.1016/S0046-8177(99)90160-0 / Hum Pathol. / The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens. by Costes (1999)
  19. 10.1083/jcb.133.2.405 / J Cell Biol. / Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican. by Steinfeld (1996)
  20. 10.1046/j.1365-2141.2000.02364.x / Br J Haematol. / Insulin-like growth factor induces the survival and proliferation of myeloma cells through an IL-6-independent transduction pathway. by Ferlin (2000)
  21. 10.4049/jimmunol.159.1.487 / J Immunol. / A role for insulin-like growth factor in the regulation of IL-6- responsive human myeloma cell line growth. by Jelinek (1997)
  22. 10.1182/blood.V88.6.2250.bloodjournal8862250 / Blood. / Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. by Georgii-Hemming (1996)
  23. 10.1182/blood.V83.12.3654.3654 / Blood. / Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. by Zhang (1994)
  24. 10.1182/blood.V91.12.4727 / Blood. / A gp130 interleukin-6 transducer-dependent SCID model of human multiple myeloma. by Rebouissou (1998)
  25. 10.4049/jimmunol.163.1.514 / J Immunol. / Induced expression of B7–1 on myeloma cells following retroviral gene transfer results in tumor-specific recognition by cytotoxic T cells. by Tarte (1999)
  26. 10.1016/S0022-1759(97)00056-2 / J Immunol Methods. / Large scale and clinical grade purification of syndecan-1+ malignant plasma cells. by Sun (1997)
  27. {'key': '2020021223254219100_B27', 'first-page': '609', 'article-title': 'Analysis of the B-cell compartment in plasma cell leukemia and multiple myeloma: immunoglobulin gene rearrangement of EBV-infected B cell lines.', 'volume': '7', 'author': 'Commes', 'year': '1993', 'journal-title': 'Leukemia.'} / Leukemia. / Analysis of the B-cell compartment in plasma cell leukemia and multiple myeloma: immunoglobulin gene rearrangement of EBV-infected B cell lines. by Commes (1993)
  28. {'key': '2020021223254219100_B28', 'first-page': '514a', 'article-title': 'Generation of polyclonal plasma cells from peripheral blood B cells: how to get a normal counterpart of malignant plasma cells [abstract].', 'volume': '96', 'author': 'Tarte', 'year': '2000', 'journal-title': 'Blood.'} / Blood. / Generation of polyclonal plasma cells from peripheral blood B cells: how to get a normal counterpart of malignant plasma cells [abstract]. by Tarte (2000)
  29. 10.1073/pnas.95.25.14863 / Proc Natl Acad Sci U S A. / Cluster analysis and display of genome-wide expression patterns. by Eisen (1998)
  30. 10.1046/j.1365-2141.2000.02127.x / Br J Haematol. / JAK2 tyrosine kinase inhibitor tyrphostin AG490 down-regulates the MAPK and STAT pathways and induces apoptosis in myeloma cells. by De Vos (2000)
  31. 10.1002/(SICI)1097-0142(19990701)86:1<43::AID-CNCR8>3.0.CO;2-D / Cancer. / Synthesis and secretion of the anticoagulant protein S and coexpression of the Tyro3 receptor in human lung carcinoma cells. by Wimmel (1999)
  32. {'key': '2020021223254219100_B32', 'first-page': '70', 'article-title': 'Cytokines, cytokine receptors and signal transduction in human multiple myeloma.', 'volume-title': 'Myeloma: Biology and Management. Oxford', 'author': 'Klein', 'year': '1998'} / Myeloma: Biology and Management. Oxford / Cytokines, cytokine receptors and signal transduction in human multiple myeloma. by Klein (1998)
  33. 10.1182/blood.V91.1.3 / Blood. / Multiple myeloma: increasing evidence for a multistep transformation process. by Hallek (1998)
  34. 10.1002/eji.1830240825 / Eur J Immunol. / Lymphotoxin acts as an autocrine growth factor for Epstein-Barr virus-transformed B cells and differentiated Burkitt lymphoma cell lines. by Gibbons (1994)
  35. 10.1084/jem.177.3.763 / J Exp Med. / Lymphotoxin is an autocrine growth factor for Epstein-Barr virus-infected B cell lines. by Estrov (1993)
  36. 10.1128/JVI.64.6.3033-3041.1990 / J Virol. / Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells. by Tosato (1990)
  37. {'key': '2020021223254219100_B37', 'first-page': '65', 'article-title': 'Tumor necrosis factor is a survival and proliferation factor for human myeloma cells.', 'volume': '10', 'author': 'Jourdan', 'year': '1999', 'journal-title': 'Eur Cytokine Netw.'} / Eur Cytokine Netw. / Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. by Jourdan (1999)
  38. 10.1182/blood.V74.4.1266.1266 / Blood. / Production of cytokines by bone marrow cells obtained from patients with multiple myeloma. by Lichtenstein (1989)
  39. 10.1111/j.1365-2141.1993.tb03341.x / Br J Haematol. / Cytokine gene expression in human multiple myeloma. by Portier (1993)
  40. {'key': '2020021223254219100_B40', 'first-page': '301', 'article-title': 'Interleukin 1 and interleukin 1 receptors in human B-cell lines.', 'volume': '8', 'author': 'Bertoglio', 'year': '1989', 'journal-title': 'Lymphokine Res.'} / Lymphokine Res. / Interleukin 1 and interleukin 1 receptors in human B-cell lines. by Bertoglio (1989)
  41. {'key': '2020021223254219100_B41', 'first-page': '3378', 'article-title': 'Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas.', 'volume': '85', 'author': 'Gruss', 'year': '1995', 'journal-title': 'Cytokines Mol Ther.'} / Cytokines Mol Ther. / Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. by Gruss (1995)
  42. 10.1002/hon.2900130302 / Hematol Oncol. / IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell lines: promotion of IL6 receptor expression by EBV. by Klein (1995)
  43. 10.1074/jbc.273.19.11799 / J Biol Chem. / Differential myeloma cell responsiveness to interferon-alpha correlates with differential induction of p19(INK4d) and cyclin D2 expression. by Arora (1998)
  44. 10.1016/S0889-8588(05)70117-9 / Hematol Oncol Clin North Am. / Mechanisms of myeloma cell growth control. by Jelinek (1999)
  45. 10.1080/00313029700169744 / Pathology. / New insights into the control of cell growth: the role of the AxI family. by Crosier (1997)
  46. 10.1128/MCB.11.10.5016 / Mol Cell Biol. / axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. by O'Bryan (1991)
  47. 10.1074/jbc.270.12.6872 / J Biol Chem. / Mouse mammary tumors express elevated levels of RNA encoding the murine homology of SKY, a putative receptor tyrosine kinase. by Taylor (1995)
  48. 10.1182/blood.V95.2.633 / Blood. / Transforming activity of receptor tyrosine kinase tyro3 is mediated, at least in part, by the PI3 kinase-signaling pathway. by Lan (2000)
  49. 10.1128/MCB.19.2.1401 / Mol Cell Biol. / A single amino acid substitution in the v-Eyk intracellular domain results in activation of Stat3 and enhances cellular transformation. by Besser (1999)
  50. 10.1016/S1074-7613(00)80011-4 / Immunity. / Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. by Catlett-Falcone (1999)
  51. 10.1016/S0145-2126(99)00075-2 / Leuk Res. / Expression of the growth arrest-specific gene 6 (GAS6) in leukemia and lymphoma cell lines. by Dirks (1999)
  52. {'key': '2020021223254219100_B52', 'first-page': '1219', 'article-title': 'GAS6, the ligand of Axl and Rse receptors, is expressed in hematopoietic tissue but lacks mitogenic activity.', 'volume': '25', 'author': 'Avanzi', 'year': '1997', 'journal-title': 'Exp Hematol.'} / Exp Hematol. / GAS6, the ligand of Axl and Rse receptors, is expressed in hematopoietic tissue but lacks mitogenic activity. by Avanzi (1997)
  53. 10.2741/A241 / Front Biosci. / Structure and function of heparin-binding EGF-like growth factor (HB-EGF). by Davis-Fleischer (1998)
  54. 10.1093/emboj/16.6.1268 / EMBO J. / Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. by Elenius (1997)
  55. 10.1038/30012 / Nature. / Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. by Qiu (1998)
  56. 10.1172/JCI4105 / J Clin Invest. / The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. by Kleeff (1998)
  57. 10.1073/pnas.96.20.11023 / Proc Natl Acad Sci U S A. / How the protease thrombin talks to cells. by Coughlin (1999)
  58. 10.1074/jbc.272.23.14713 / J Biol Chem. / Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor receptor activation. by Subramanian (1997)
  59. {'key': '2020021223254219100_B59', 'first-page': '335', 'article-title': 'Activation molecules on human myeloma cells.', 'volume': '246', 'author': 'Klein', 'year': '1999', 'journal-title': 'Curr Top Microbiol Immunol.'} / Curr Top Microbiol Immunol. / Activation molecules on human myeloma cells. by Klein (1999)
  60. 10.1182/blood.V95.2.388 / Blood. / Serum syndecan-1: a new independent prognostic marker in multiple myeloma [published erratum appears in Blood. 2000 Apr 1;95(7):2197]. by Seidel (2000)
  61. 10.1038/47260 / Nature. / EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. by Prenzel (1999)
  62. 10.1038/nm0898-909 / Nat Med. / Thrombin receptor overexpression in malignant and physiological invasion processes. by Even-Ram (1998)
  63. 10.1146/annurev.immunol.18.1.217 / Annu Rev Immunol. / The biology of chemokines and their receptors. by Rossi (2000)
  64. 10.1126/science.283.5403.845 / Science. / Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. by Peled (1999)
  65. 10.1073/pnas.95.16.9448 / Proc Natl Acad Sci U S A. / Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. by Ma (1998)
  66. {'key': '2020021223254219100_B66', 'first-page': '473a', 'article-title': 'The chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates chemotaxis to monocyte chemotactic proteins MCP-1, 2 and 3 [abstract].', 'volume': '96', 'author': 'Vande Broek', 'year': '2000', 'journal-title': 'Blood.'} / Blood. / The chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates chemotaxis to monocyte chemotactic proteins MCP-1, 2 and 3 [abstract]. by Vande Broek (2000)
  67. {'key': '2020021223254219100_B67', 'first-page': '550a', 'article-title': 'Myeloma cells homing to the bone marrow is directed by CXCR4/SDF-1 interactions [abstract].', 'volume': '96', 'author': 'Woodliff', 'year': '2000', 'journal-title': 'Blood.'} / Blood. / Myeloma cells homing to the bone marrow is directed by CXCR4/SDF-1 interactions [abstract]. by Woodliff (2000)
  68. 10.1126/science.281.5382.1438 / Science. / How a growth control path takes a wrong turn to cancer [published erratum appears in Science. 1998 Sep 18;281:1809]. by Pennisi (1998)
  69. 10.1074/jbc.271.42.26131 / J Biol Chem. / Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis. by Hoang (1996)
  70. 10.1016/S0092-8674(00)81922-4 / Cell. / Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. by Wang (1997)
  71. 10.1182/blood.V93.8.2431 / Blood. / Notch as a mediator of cell fate determination in hematopoiesis: evidence and speculation. by Milner (1999)
  72. 10.1016/0092-8674(91)90111-B / Cell. / TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. by Ellisen (1991)
  73. 10.1126/science.7716513 / Science. / Notch signaling. by Artavanis-Tsakonas (1995)
  74. 10.1084/jem.183.5.2283 / J Exp Med. / Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. by Pear (1996)
  75. 10.1182/blood.V85.4.863.bloodjournal854863 / Blood. / Interleukin-6 in human multiple myeloma. by Klein (1995)
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 8:46 a.m.)
Deposited 2 years, 4 months ago (April 23, 2023, 4:11 p.m.)
Indexed 1 day, 15 hours ago (Sept. 3, 2025, 6:01 a.m.)
Issued 24 years, 1 month ago (Aug. 1, 2001)
Published 24 years, 1 month ago (Aug. 1, 2001)
Published Print 24 years, 1 month ago (Aug. 1, 2001)
Funders 0

None

@article{De_Vos_2001, title={Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays}, volume={98}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v98.3.771}, DOI={10.1182/blood.v98.3.771}, number={3}, journal={Blood}, publisher={American Society of Hematology}, author={De Vos, John and Couderc, Guilhem and Tarte, Karin and Jourdan, Michel and Requirand, Guilhem and Delteil, Marie-Claude and Rossi, Jean-François and Mechti, Nadir and Klein, Bernard}, year={2001}, month=aug, pages={771–780} }