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[Cancer Research 59, 728-733, February 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 728-733, February 1, 1999]
© 1999 American Association for Cancer Research

Tumor Biology

Expression of Vascular Endothelial Growth Factor and Its Receptors in Hematopoietic Malignancies1

William T. Bellamy2, Lynne Richter, Yvette Frutiger and Thomas M. Grogan

Department of Pathology, University of Arizona, Tucson, Arizona 85724

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by acting as a potent inducer of vascular permeability as well as serving as a specific endothelial cell mitogen. The importance of angiogenic factors such as VEGF, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. We examined the expression of mRNA and protein for VEGF in 12 human hematopoietic tumor cell lines, representing multiple lineages and diseases, including leukemia, lymphoma, and multiple myeloma. Our results revealed that VEGF message was expressed in these cells and that the corresponding protein was secreted into the extracellular environment. Five of the 12 cell lines were also found to express the Flt-1 receptor for VEGF at a moderate to strong level, suggesting an autocrine pathway. When human vascular endothelial cells were exposed to recombinant human VEGF, there was an increase in the mRNA for several hematopoietic growth factors including macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin 6. Plasma cells in the bone marrow from patients diagnosed with multiple myeloma were found to express VEGF, whereas both the Flt-1 and KDR high affinity VEGF receptors were observed to be markedly elevated in the normal bone marrow myeloid and monocytic cells surrounding the tumor. These data raise the possibility that VEGF may play a role in the growth of hematopoietic neoplasms such as multiple myeloma through either a paracrine or an autocrine mechanism.




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The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies
Oncologist, October 1, 2001; 6(2008): 32 - 39.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
T. Hayashibara, Y. Yamada, T. Miyanishi, H. Mori, T. Joh, T. Maeda, N. Mori, T. Maita, S. Kamihira, and M. Tomonaga
Vascular Endothelial Growth Factor and Cellular Chemotaxis: A Possible Autocrine Pathway in Adult T-Cell Leukemia Cell Invasion
Clin. Cancer Res., September 1, 2001; 7(9): 2719 - 2726.
[Abstract] [Full Text] [PDF]

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M. H. Mangi, W. T. Bellamy, T. M. Grogan, and A. F. List
Misleading information about ALIP and VEGF in myelodysplasia
Blood, August 15, 2001; 98(4): 1272 - 1273.
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J. De Vos, G. Couderc, K. Tarte, M. Jourdan, G. Requirand, M.-C. Delteil, J.-F. Rossi, N. Mechti, and B. Klein
Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays
Blood, August 1, 2001; 98(3): 771 - 780.
[Abstract] [Full Text] [PDF]

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K. Podar, Y.-T. Tai, F. E. Davies, S. Lentzsch, M. Sattler, T. Hideshima, B. K. Lin, D. Gupta, Y. Shima, D. Chauhan, et al.
Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration
Blood, July 15, 2001; 98(2): 428 - 435.
[Abstract] [Full Text] [PDF]

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 Cell Growth Differ.Home page
M. S. Irwin and W. G. Kaelin
p53 Family Update: p73 and p63 Develop Their Own Identities
Cell Growth Differ., July 1, 2001; 12(7): 337 - 349.
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R. M. Mesters, T. Padro, R. Bieker, M. Steins, M. Kreuter, M. Goner, S. Kelsey, P. Scigalla, W. Fiedler, T. Buchner, et al.
Stable remission after administration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refractory acute myeloid leukemia
Blood, July 1, 2001; 98(1): 241 - 243.
[Abstract] [Full Text] [PDF]

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A. R. Kini, L. C. Peterson, M. S. Tallman, and M. W. Lingen
Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid
Blood, June 15, 2001; 97(12): 3919 - 3924.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
S. Wellmann, T. Taube, K. Paal, H. Graf v. Einsiedel, W. Geilen, G. Seifert, C. Eckert, G. Henze, and K. Seeger
Specific Reverse Transcription-PCR Quantification of Vascular Endothelial Growth Factor (VEGF) Splice Variants by LightCycler Technology
Clin. Chem., April 1, 2001; 47(4): 654 - 660.
[Abstract] [Full Text] [PDF]

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A. Ferrajoli, T. Manshouri, Z. Estrov, M. J. Keating, S. O’Brien, S. Lerner, M. Beran, H. M. Kantarjian, E. J. Freireich, and M. Albitar
High Levels of Vascular Endothelial Growth Factor Receptor-2 Correlate with Shortened Survival in Chronic Lymphocytic Leukemia
Clin. Cancer Res., April 1, 2001; 7(4): 795 - 799.
[Abstract] [Full Text]

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D. J. Brat and E. G. Van Meir
Glomeruloid Microvascular Proliferation Orchestrated by VPF/VEGF : A New World of Angiogenesis Research
Am. J. Pathol., March 1, 2001; 158(3): 789 - 796.
[Full Text] [PDF]

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B. D. Smolich, H. A. Yuen, K. A. West, F. J. Giles, M. Albitar, and J. M. Cherrington
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, March 1, 2001; 97(5): 1413 - 1421.
[Abstract] [Full Text] [PDF]

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W. T. Bellamy, L. Richter, D. Sirjani, C. Roxas, B. Glinsmann-Gibson, Y. Frutiger, T. M. Grogan, and A. F. List
Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes
Blood, March 1, 2001; 97(5): 1427 - 1434.
[Abstract] [Full Text] [PDF]

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 ASH Education BookHome page
W. S. Dalton, P. L. Bergsagel, W. M. Kuehl, K. C. Anderson, and J. L. Harousseau
Multiple Myeloma
Hematology, January 1, 2001; 2001(1): 157 - 177.
[Abstract] [Full Text] [PDF]

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R. J. Klasa, A. F. List, and B. D. Cheson
Rational Approaches to Design of Therapeutics Targeting Molecular Markers
Hematology, January 1, 2001; 2001(1): 443 - 462.
[Abstract] [Full Text] [PDF]

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R. A. Mesa, C. A. Hanson, S. V. Rajkumar, G. Schroeder, and A. Tefferi
Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia
Blood, November 15, 2000; 96(10): 3374 - 3380.
[Abstract] [Full Text] [PDF]

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T. Hideshima, D. Chauhan, Y. Shima, N. Raje, F. E. Davies, Y.-T. Tai, S. P. Treon, B. Lin, R. L. Schlossman, P. Richardson, et al.
Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy
Blood, November 1, 2000; 96(9): 2943 - 2950.
[Abstract] [Full Text] [PDF]

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A. Aguayo, H. Kantarjian, T. Manshouri, C. Gidel, E. Estey, D. Thomas, C. Koller, Z. Estrov, S. O'Brien, M. Keating, et al.
Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes
Blood, September 15, 2000; 96(6): 2240 - 2245.
[Abstract] [Full Text] [PDF]

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G. J. Roboz, S. Dias, G. Lam, W. J. Lane, S. L. Soignet, R. P. Warrell Jr, and S. Rafii
Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis
Blood, August 15, 2000; 96(4): 1525 - 1530.
[Abstract] [Full Text] [PDF]

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S. V. Rajkumar, T. Leong, P. C. Roche, R. Fonseca, A. Dispenzieri, M. Q. Lacy, J. A. Lust, T. E. Witzig, R. A. Kyle, M. A. Gertz, et al.
Prognostic Value of Bone Marrow Angiogenesis in Multiple Myeloma
Clin. Cancer Res., August 1, 2000; 6(8): 3111 - 3116.
[Abstract] [Full Text]

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A. Aguayo, S. O'Brien, M. Keating, T. Manshouri, C. Gidel, B. Barlogie, M. Beran, C. Koller, H. Kantarjian, and M. Albitar
Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia
Blood, July 15, 2000; 96(2): 768 - 770.
[Abstract] [Full Text] [PDF]

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F. Bertolini, L. Fusetti, P. Mancuso, A. Gobbi, C. Corsini, P. F. Ferrucci, G. Martinelli, and G. Pruneri
Endostatin, an antiangiogenic drug, induces tumor stabilization after chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade non-Hodgkin lymphoma
Blood, July 1, 2000; 96(1): 282 - 287.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. Fusetti, G. Pruneri, A. Gobbi, C. Rabascio, N. Carboni, F. Peccatori, G. Martinelli, and F. Bertolini
Human Myeloid and Lymphoid Malignancies in the Non-Obese Diabetic/Severe Combined Immunodeficiency Mouse Model: Frequency of Apoptotic Cells in Solid Tumors and Efficiency and Speed of Engraftment Correlate with Vascular Endothelial Growth Factor Production
Cancer Res., May 1, 2000; 60(9): 2527 - 2534.
[Abstract] [Full Text]

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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]

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 The OncologistHome page
L. Rosen
Antiangiogenic Strategies and Agents in Clinical Trials
Oncologist, April 1, 2000; 5(90001): 20 - 27.
[Abstract] [Full Text]

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N. Munshi, J. E. Groopman, P. S. Gill, and R. K. Ganju
c-Src Mediates Mitogenic Signals and Associates with Cytoskeletal Proteins upon Vascular Endothelial Growth Factor Stimulation in Kaposi's Sarcoma Cells
J. Immunol., February 1, 2000; 164(3): 1169 - 1174.
[Abstract] [Full Text] [PDF]

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K. Kuramoto, T. Uesaka, A. Kimura, M. Kobayashi, H. Watanabe, and O. Katoh
ZK7, a Novel Zinc Finger Gene, Is Induced by Vascular Endothelial Growth Factor and Inhibits Apoptotic Death in Hematopoietic Cells
Cancer Res., January 1, 2000; 60(2): 425 - 430.
[Abstract] [Full Text]

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 ASH Education BookHome page
E. Hellstrom-Lindberg, C. Willman, A. J. Barrett, and Y. Saunthararajah
Achievements in Understanding and Treatment of Myelodysplastic Syndromes
Hematology, January 1, 2000; 2000(1): 110 - 132.
[Abstract] [Full Text] [PDF]

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J. W. Hussong, G. M. Rodgers, and P. J. Shami
Evidence of increased angiogenesis in patients with acute myeloid leukemia
Blood, January 1, 2000; 95(1): 309 - 313.
[Abstract] [Full Text] [PDF]

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N. Raje and K. Anderson
Thalidomide -- A Revival Story
N. Engl. J. Med., November 18, 1999; 341(21): 1606 - 1609.
[Full Text]


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