The role of VEGF in normal and neoplastic hematopoiesis

Journal of Molecular Medicine

Volumn 81, Issue 1, 2003, Pages 20-31

  Gerber, Hans Peter ^a   Ferrara, Napoleone ^a  

^a GENENTECH INC   (United States)

Author keywords

Angiogenesis; Hematopoiesis; Internal external autocrine loop

Indexed keywords

VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ANGIOGENESIS; AUTOCRINE EFFECT; CELL LINEAGE; CELL TYPE; EMBRYO DEVELOPMENT; ENDOTHELIUM CELL; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; LEUKEMIA; LYMPHOMA; MYELODYSPLASTIC SYNDROME; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; PARACRINE SIGNALING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

EID: 0037280306     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00109-002-0397-4     Document Type: Review

References (88)

1. Gerber HP, Malik AK, Solar GP, Sherman D, Liang XH, Meng G, Hong K, Marsters JC, Ferrara N (2002) VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature 417:954-958
2. Browder TM, Abrams JS, Wong PM, Nienhuis AW (1989) Mechanism of autocrine stimulation in hematopoietic cells producing interleukin-3 after retrovirus-mediated gene transfer. Mol Cell Biol 9:204-213
3. Gerber HP, Ferrara N (2000) Angiogenesis and bone growth. Trends Cardiovasc Med 10:223-228
4. Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Pietrzkowski Z, Kowalska MA, Gewirtz AM, Emerson SG, Ratajczak MZ (2001) Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblast, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 97:3075-3085
5. Ferrara N, Houck K, Jakeman L, Leung DW (1992) Molecular and biological properties of the vascular endothelial growth family of proteins. Endocr Rev 13:18-32
6. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW (1991) The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5:1806-1814
7. Poltorak Z, Cohen T, Sivan R, Kandelis Y, Spira G, Vlodavsky I, Keshet E, Neufeld G (1997) VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix. J Biol Chem 272:7151-7158
8. Park JE, Keller, H.-A, Ferrara N (1993) The vascular endothelial growth factor isoforms (VEGF): Differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4:1317-1326
9. Grunstein J, Masbad JJ, Hickey R, Giordano F, Johnson RS (2000) Isoforms of vascular endothelial growth factor act in a coordinate fashion To recruit and expand tumor vasculature. Mol Cell Biol 20:7282-7891
10. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029-1039
11. Koch AE, Harlow L, Haines GK, Amento EP, Unemori EN, Wong, W.-L, Pope RM, Ferrara N (1994) Vascular endothelial growth factor: a cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 152:4149-4156
12. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2:1096-1103
13. Ferrara N, Carver Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439-442
14. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435-439
15. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H, Scholz D, Acker T, DiPalma T, Dewerchin M, Noel A, Stalmans I, Barra A, Blacher S, Vandendriessche T, Ponten A, Eriksson U, Plate KH, Foidart JM, Schaper W, Charnock-Jones DS, Hicklin DJ, Herbert JM, Collen D, Persico MG (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575-583
16. Aase K, von Euler G, Li X, Ponten A, Thoren P, Cao R, Cao Y, Olofsson B, Gebre-Medhin S, Pekny M, Alitalo K, Betsholtz C, Eriksson U (2001) Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect. Circulation 104:358-364
17. Alitalo K, Carmeliet P (2002) Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cells 1:219-227
18. Midy V, Plouet J (1994) Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem Biophys Res Commun 199:380-366
19. Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K, Van Dorpe J, Hellings P, Gorselink M, Heymans S, Theilmeier G, Dewerchin M, Laudenbach V, Vermylen P, Raat H, Acker T, Vleminckx V, Van Den Bosch L, Cashman N, Fujisawa H, Drost MR, Sciot R, Bruyninckx F, Hicklin DJ, Ince C, Gressens P, Lupu F, Plate KH, Robberecht W, Herbert JM, Collen D, Carmeliet P (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 28:131-138
20. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92:735-745
21. Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56:794-814
22. Gerber HP, Dixit V, Ferrara N (1998) Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 273:13313-13316
23. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, Ferrara N (1998) Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 273:30336-30343
24. Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, Pelletier N, Ferrara N (2001) Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 276:3222-3230
25. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62-66
26. Shalaby F, Ho J, Stanford WL, Fischer KD, Schuh AC, Schwartz L, Bernstein A, Rossant J (1997) A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Cell 89:981-990
27. Hidaka M, Stanford WL, Bernstein A (1999) Conditional requirement for the Flk-1 receptor in the in vitro generation of early hematopoietic cells. Proc Natl Acad Sci USA 96:7370-7375
28. Fong GH, Rossant J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66-70
29. Fong GH, Zhang L, Bryce DM, Peng J (1999) Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development 126:3015-3025
30. Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M (1998) Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A 95:9349-9354
31. Shibuya M (2001) Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1). Int J Biochem Cell Biol 33:409-420
32. Lasky LA (1996) Hematopoiesis: wandering progenitor cells. Curr Biol 6:1238-1240
33. Ohneda O, Fennie C, Zheng Z, Donahue C, La H, Villacorta R, Cairns B, Lasky LA (1998) Hematopoietic stem cell maintenance and differentiation are supported by embryonic aorta-gonad-mesonephros region-derived endothelium. Blood 92:908-919
34. Robertson S, Kennedy M, Keller G (1999) Hematopoietic commitment during embryogenesis. Ann N Y Acad Sci 872:9-15-
35. Bautz F, Rafii S, Kanz L, Mohle R (2000) Expression and secretion of vascular endothelial growth factor-A by cytokine-stimulated hematopoietic progenitor cells. Possible role in the hematopoietic microenvironment. Exp Hematol 28:700-706
36. Kabrun N, Buhring HJ, Choi K, Ullrich A, Risau W, Keller G (1997) Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 124:2039-2048
37. Ziegler BL, Valtieri M, Porada GA, De Maria R, Muller R, Masella B, Gabbianelli M, Casella I, Pelosi E, Bock T, Zanjani ED, Peschle C (1999) KDR receptor: a key marker defining hematopoietic stem cells. Science 285:1553-1558
38. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, Carbone DP (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150-4166
39. Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MA, Rafii S (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193:1005-1014
40. Haruta H, Nagata Y, Todokoro K (2001) Role of Flk-1 in mouse hematopoietic stem cells. FEBS Lett 507:45-48
41. Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrilcx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8:841-849
42. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194-1201
43. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964-3972
44. Kalka C, Masuda H, Takahashi T, Gordon R, Tepper O, Gravereaux E, Pieczek A, Iwaguro H, Hayashi SI, Isner JM, Asahara T (2000) Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 86:1198-1202
45. Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA (2000) Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest 106:571-578
46. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434-438
47. Luttun A, Brusselmans K, Fukao H, Tjwa M, Ueshima S, Herbert JM, Matsuo O, Collen D, Carmeliet P, Moons L (2002) Loss of placental growth factor protects mice against vascular permeability in pathological conditions. Biochem Biophys Res Commun 295:428-434
48. Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN, Byrne BJ, Vaught T, Spoerri PE, Peck AB, Scott EW (2002) Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovacularization. Nat Med 8:607-612
49. Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P (2002) Revascularization of ischemic tissues by P1GF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 1:1
50. Eriksson A, Cao R, Pawliuk R, Berg SM, Tsang M, Zhou D, Fleet C, Tritsaris K, Dissing S, Leboulch P, Cao Y (2002) Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive P1GF-1/VEGF heterodimers. Cancer Cells 1:99-108
51. Dias S, Hattori K, Zhu Z, Heissig B, Choy M, Lane W, Wu Y, Chadburn A, Hyjek E, Gill M, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest 106:511-521
52. Young DC, Wagner K, Griffin JD (1987) Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia. J Clin Invest 79:100-106
53. Oster W, Lindemann A, Mertelsmann R, Herrmann F (1988) Regulation of gene expression of M-, G-, GM-, and multi-CSF in normal and malignant hematopoietic cells. Blood Cells 14:443-462
54. Cheng GY, Kelleher CA, Miyauchi J, Wang C, Wong G, Clark SC, McCulloch EA, Minden MD (1988) Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with acute myeloblastic leukemia. Blood 71:204-208
55. Cozzolino F, Rubartelli A, Aldinucci D, Sitia R, Torcia M, Shaw A, Di Guglielmo R (1989) Interleukin 1 as an autocrine growth factor for acute myeloid leukemia cells. Proc Natl Acad Sci U S A 86:2369-2373
56. Tinhofer I, Marschitz I, Henn T, Egle A, Greil R (2000) Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood 95:610-618
57. Lu C, Kerbel RS (1993) Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J Cell Biol 120:1281-1288
58. Kitani A, Hara M, Hirose T, Harigai M, Suzuki K, Kawakami M, Kawaguchi Y, Hidaka T, Kawagoe M, Nakamura H (1992) Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clin Exp Immunol 88:75-83
59. Bellamy WT, Richter L, Frutiger Y, Grogan TM (1999) Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res 59:728-733
60. Fiedler W, Graeven U, Ergun S, Verago S, Kilic N, Stockschlader M, Hossfeld DK (1997) Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood 89:1870-1875
61. Bellamy WT, Richter L, Sirjani D, Roxas C, Glinsmann-Gibson B, Frutiger Y, Grogan TM, List AF (2001) Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 97:1427-1434
62. Ratajczak MZ, Ratajczak J, Machalinski B, Majka M, Marlicz W, Carter A, Pietrzkowski Z, Gewirtz AM (1998) Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (P1GF) in regulating human haemopoietic cel growth. Br J Haematol 103:969-979
63. Katoh O, Takahashi T, Oguri T, Kuramoto K, Mihara K, Kobayashi M, Hirata S, Watanabe H (1998) Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor. Cancer Res 58:5565-5569
64. Smolich BD, Yuen HA, West KA, Giles FJ, Albitar M, Cherrington JM (2001) The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 97:1413-1421
65. Lin B, Podar K, Gupta D, Tai YT, Li S, Weller E, Hideshima T, Lentzsch S, Davies F, Li C, Weisberg E, Schlossman RL, Richardson PG, Griffin JD, Wood J, Munshi NC, Anderson KC (2002) The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. Cancer Res 62:5019-5026
66. Mesters RM, Padro T, Bieker R, Steins M, Kreuter M, Goner M, Kelsey S, Scigalla P, Fiedler W, Buchner T, Berdel WE (2001) Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia. Blood 98:241-243
67. Dias S, Hattori K, Heissig B, Zhu Z, Wu Y, Witte L, Hicklin DJ, Tateno M, Bohlen P. Moore MA, Rafii S (2001) Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. Proc Natl Acad Sci U S A 98:10857-10862
68. Goodell MA, Jackson KA, Majka SM, Mi T, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK (2001) Stem cell plasticity in muscle and bone marrow. Ann N Y Acad Sci 938:208-218-
69. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229-1234
70. Padro T, Bieker R, Ruiz S, Steins M, Retzlaff S, Burger H, Buchner T, Kessler T, Herrera F, Kienast J, Muller-Tidow C, Serve H, Berdel WE, Mesters RM (2002) Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia. Leukemia 16:1302-1310
71. Bont ES de, Rosati S, Jacobs S, Kamps WA, Vellenga E (2001) Increased bone marrow vascularization in patients with acute myeloid leukaemia: a possible role for vascular endothelial growth factor. Br J Haematol 113:296-304
72. Lundberg LG, Lerner R, Sundelin P, Rogers R, Folkman J, Palmblad J (2000) Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity. Am J Pathol 157:15-19
73. Fielder W, Graeven U, Ergun S, Verago S, Kilic N, Stockschlader M, Hossfeld DK (1997) Expression of FLT4 and its ligand VEGF-C in acute myeloid leukemia. Leukemia 11:1234-1237
74. Aguayo A, Estey E, Kantarjian H, Mansouri T, Gidel C, Keating M, Giles F, Estrov Z, Barlogie B, Albitar M (1999) Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. Blood 94:3717-3721
75. Verstovsek S, Estey E, Manshouri T, Giles FJ, Cortes J, Beran M, Rogers A, Keating M, Kantarjian H, Albitar M (2002) Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome. Br J Haematol 118:151-156
76. Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin's lymphoma. Blood 90:3167-3172
77. Verstovsek S, Kantarjian H, Manshouri T, Cortes J, Giles FJ, Rogers A, Albitar M (2002) Prognostic significance of cellular vascular endothelial growth factor expression in chronic phase chronic myeloid leukemia. Blood 99:2265-2267
78. Young DC, Griffin JD (1986) Autocrine secretion of GM-CSF in acute myeloblastic leukemia. Blood 68:1178-1181
79. Rambaldi A, Wakamiya N, Vellenga E, Horiguchi J, Warren MK, Kufe D, Griffin JD (1988) Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. J Clin Invest 81:1030-1035
80. Attias D, Grunberger T, Vanek W, Estrov Z, Cohen A, Lau R, Freedman MH (1995) B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts. Leukemia 9:884-888
81. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, et al (1988) Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332:83-85
82. O'Connell MA, Cleere R, Long A, O'Neill LA, Kelleher D (1995) Cellular proliferation and activation of NF kappa B are induced by autocrine production of tumor necrosis factor alpha in the human T lymphoma line HuT 78. J Biol Chem 270:7399-7404
83. Gibbons DL, Rowe M, Cope AP, Feldmann M, Brennan FM (1994) Lymphotoxin acts as an autocrine growth factor for Epstein-Barr virus-transformed B cells and differentiated Burkitt lymphoma cell lines. Eur J Immunol 24:1879-1885
84. Schwab G, Siegall CB, Aarden LA, Neckers LM, Nordan RP (1991) Characterization of an interleukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266. Blood 77:587-593
85. Lang RA, Metcalf D, Cuthbertson RA, Lyons I, Stanley E, Kelso A, Kannourakis G, Williamson DJ, Klintworth GK, Gonda TJ, et al (1987) Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulation of macrophages, blindness, and a fatal syndrome of tissue damage. Cell 51:675-686
86. Huang SS, Huang JS (1988) Rapid turnover of the platelet-derived growth factor receptor in sis-transformed cells and reversal by suramin. Implications for the mechanism of autocrine transformation. J Biol Chem 263:12608-12618
87. Georgii-Hemming P, Wiklund HJ, Ljunggren O, Nilsson K (1996) Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. Blood 88:2250-2258
88. Villunger A, Egle A, Kos M, Hittmair A, Maly K, Greil R (1996) Constituents of autocrine IL-6 loops in myeloma cell lines and their targeting for suppression of neoplastic growth by antibody strategies. Int J Cancer 65:498-505