Clinical Cancer Research CR Balducci Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eggert, A.
Right arrow Articles by Himelstein, B. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eggert, A.
Right arrow Articles by Himelstein, B. P.
Clinical Cancer Research Vol. 6, 1900-1908, May 2000
© 2000 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

High-Level Expression of Angiogenic Factors Is Associated with Advanced Tumor Stage in Human Neuroblastomas1

Angelika Eggert2, Naohiko Ikegaki, Janet Kwiatkowski, Huaqing Zhao, Garrett M. Brodeur and Bruce P. Himelstein

Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. Neuroblastoma (NB) is a common pediatric tumor of neural crest origin, which is biologically and clinically heterogeneous. Increased tumor vascular index correlates with poor outcome of NB. To determine which angiogenic factors contribute to NB angiogenesis and thereby support tumor progression, we examined the expression of eight angiogenic factors [vascular endothelial growth factor (VEGF), VEGF-B, VEGF-C, basic fibroblast growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor {alpha}, and platelet-derived growth factor (PDGF)] by semiquantitative RT-PCR in 37 NB primary tumors and in 22 NB cell lines. We also analyzed the relationship between angiogenic factor expression and clinicopathological factors as well as patient survival. All eight angiogenic factors examined were expressed at various levels in NB cell lines and tumors, suggesting their involvement in NB angiogenesis. The expression levels of most angiogenic factors were correlated with each other, suggesting their synergy in regulating the angiogenic process. Significantly higher expression levels of VEGF, VEGF-B, VEGF-C, basic fibroblast growth factor, Ang-2, transforming growth factor {alpha}, and PDGF-A (P < 0.0001–0.026) were found in advanced-stage tumors (stages 3 and 4) compared with low-stage tumors (stages 1, 2, and 4S). Expression of PDGF-A was significantly associated with patient survival (P = 0.04). The redundancy in angiogenic factor expression suggests that inhibition of VEGF bioactivity alone might not be a sufficient approach for antiangiogenic therapy of human NB.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
J. Ma and D. J. Waxman
Combination of antiangiogenesis with chemotherapy for more effective cancer treatment
Mol. Cancer Ther., December 1, 2008; 7(12): 3670 - 3684.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Puppo, F. Battaglia, C. Ottaviano, S. Delfino, D. Ribatti, L. Varesio, and M. C. Bosco
Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1{alpha} and -2{alpha}
Mol. Cancer Ther., July 1, 2008; 7(7): 1974 - 1984.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
W. S.N. Shim, I. A.W. Ho, and P. E.H. Wong
Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis
Mol. Cancer Res., July 1, 2007; 5(7): 655 - 665.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Peddinti, R. Zeine, D. Luca, R. Seshadri, A. Chlenski, K. Cole, B. Pawel, H. R. Salwen, J. M. Maris, and S. L. Cohn
Prominent Microvascular Proliferation in Clinically Aggressive Neuroblastoma
Clin. Cancer Res., June 15, 2007; 13(12): 3499 - 3506.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. K. Martens, K. M. Kirschner, C. Warnecke, and H. Scholz
Hypoxia-inducible Factor-1 (HIF-1) Is a Transcriptional Activator of the TrkB Neurotrophin Receptor Gene
J. Biol. Chem., May 11, 2007; 282(19): 14379 - 14388.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. R. Hsu, W. Cai, A. Veeravagu, K. A. Mohamedali, K. Chen, S. Kim, H. Vogel, L. C. Hou, V. Tse, M. G. Rosenblum, et al.
Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121/rGel
J. Nucl. Med., March 1, 2007; 48(3): 445 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q. Yang, Y. Tian, S. Liu, R. Zeine, A. Chlenski, H. R. Salwen, J. Henkin, and S. L. Cohn
Thrombospondin-1 Peptide ABT-510 Combined with Valproic Acid Is an Effective Antiangiogenesis Strategy in Neuroblastoma
Cancer Res., February 15, 2007; 67(4): 1716 - 1724.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Pezzolo, F. Parodi, M. V. Corrias, R. Cinti, C. Gambini, and V. Pistoia
Tumor Origin of Endothelial Cells in Human Neuroblastoma
J. Clin. Oncol., February 1, 2007; 25(4): 376 - 383.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. Hussein, E. J. Estlin, C. Dive, and G. W.J. Makin
Chronic hypoxia promotes hypoxia-inducible factor-1{alpha}-dependent resistance to etoposide and vincristine in neuroblastoma cells.
Mol. Cancer Ther., September 1, 2006; 5(9): 2241 - 2250.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Kosugi, A. Miyajima, E. Kikuchi, Y. Horiguchi, and M. Murai
Angiotensin II Type 1 Receptor Antagonist Candesartan as an Angiogenic Inhibitor in a Xenograft Model of Bladder Cancer.
Clin. Cancer Res., May 1, 2006; 12(9): 2888 - 2893.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Nakamura, K. C. Martin, J. K. Jackson, K. Beppu, C.-W. Woo, and C. J. Thiele
Brain-Derived Neurotrophic Factor Activation of TrkB Induces Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Factor-1{alpha} in Neuroblastoma Cells.
Cancer Res., April 15, 2006; 66(8): 4249 - 4255.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Ho, J. E. Minturn, T. Hishiki, H. Zhao, Q. Wang, A. Cnaan, J. Maris, A. E. Evans, and G. M. Brodeur
Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor
Cancer Res., November 1, 2005; 65(21): 9868 - 9875.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Shikada, Y. Yonemitsu, T. Koga, M. Onimaru, T. Nakano, S. Okano, S. Sata, K. Nakagawa, I. Yoshino, Y. Maehara, et al.
Platelet-Derived Growth Factor-AA Is an Essential and Autocrine Regulator of Vascular Endothelial Growth Factor Expression in Non-Small Cell Lung Carcinomas
Cancer Res., August 15, 2005; 65(16): 7241 - 7248.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Das, H. Yeger, R. Tsuchida, R. Torkin, M. F.W. Gee, P. S. Thorner, M. Shibuya, D. Malkin, and S. Baruchel
A Hypoxia-Driven Vascular Endothelial Growth Factor/Flt1 Autocrine Loop Interacts with Hypoxia-Inducible Factor-1{alpha} through Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 Pathway in Neuroblastoma
Cancer Res., August 15, 2005; 65(16): 7267 - 7275.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Beppu, K. Nakamura, W. M. Linehan, A. Rapisarda, and C. J. Thiele
Topotecan Blocks Hypoxia-Inducible Factor-1{alpha} and Vascular Endothelial Growth Factor Expression Induced by Insulin-Like Growth Factor-I in Neuroblastoma Cells
Cancer Res., June 1, 2005; 65(11): 4775 - 4781.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Lasorella, G. Rothschild, Y. Yokota, R. G. Russell, and A. Iavarone
Id2 Mediates Tumor Initiation, Proliferation, and Angiogenesis in Rb Mutant Mice
Mol. Cell. Biol., May 1, 2005; 25(9): 3563 - 3574.
[Abstract] [Full Text] [PDF]

Home page
 Neuro OncolHome page
B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Neuro-oncol, April 1, 2005; 7(2): 134 - 153.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
M. J. Morowitz, R. Barr, Q. Wang, R. King, N. Rhodin, B. Pawel, H. Zhao, S. A. Erickson, G. S. Sheppard, J. Wang, et al.
Methionine Aminopeptidase 2 Inhibition Is an Effective Treatment Strategy for Neuroblastoma in Preclinical Models
Clin. Cancer Res., April 1, 2005; 11(7): 2680 - 2685.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
J. FOLKMAN and S. RYEOM
Is Oncogene Addiction Angiogenesis-dependent?
Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 389 - 397.
[Abstract] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. Garcia de la Torre, I. Buley, J. A. H. Wass, D. G. Jackson, and H. E. Turner
Angiogenesis and Lymphangiogenesis in Parathyroid Proliferative Lesions
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2890 - 2896.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Tsutsumi, Y. Yonemitsu, Y. Shikada, M. Onimaru, M. Tanii, S. Okano, K. Kaneko, M. Hasegawa, M. Hashizume, Y. Maehara, et al.
Essential Role of PDGFR{alpha}-p70S6K Signaling in Mesenchymal Cells During Therapeutic and Tumor Angiogenesis In Vivo: Role of PDGFR{alpha} During Angiogenesis
Circ. Res., May 14, 2004; 94(9): 1186 - 1194.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
K. Beppu, J. Jaboine, M. S. Merchant, C. L. Mackall, and C. J. Thiele
Effect of Imatinib Mesylate on Neuroblastoma Tumorigenesis and Vascular Endothelial Growth Factor Expression
J Natl Cancer Inst, January 7, 2004; 96(1): 46 - 55.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q.-W. Yang, S. Liu, Y. Tian, H. R. Salwen, A. Chlenski, J. Weinstein, and S. L. Cohn
Methylation-associated Silencing of the Thrombospondin-1 Gene in Human Neuroblastoma
Cancer Res., October 1, 2003; 63(19): 6299 - 6310.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. L. Weinstein, H. M. Katzenstein, and S. L. Cohn
Advances in the Diagnosis and Treatment of Neuroblastoma
Oncologist, June 1, 2003; 8(3): 278 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Yokoyama, D. S. Charnock-Jones, D. Licence, A. Yanaihara, J. M. Hastings, C. M. Holland, M. Emoto, A. Sakamoto, T. Sakamoto, H. Maruyama, et al.
Expression of Vascular Endothelial Growth Factor (VEGF)-D and Its Receptor, VEGF Receptor 3, as a Prognostic Factor in Endometrial Carcinoma
Clin. Cancer Res., April 1, 2003; 9(4): 1361 - 1369.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Chlenski, S. Liu, S. E. Crawford, O. V. Volpert, G. H. DeVries, A. Evangelista, Q. Yang, H. R. Salwen, R. Farrer, J. Bray, et al.
SPARC Is a Key Schwannian-derived Inhibitor Controlling Neuroblastoma Tumor Angiogenesis
Cancer Res., December 15, 2002; 62(24): 7357 - 7363.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Tanaka, S. Ishikawa, K. Yanagihara, R. Miyahara, Y. Kawano, M. Li, Y. Otake, and H. Wada
Expression of Angiopoietins and Its Clinical Significance in Non-Small Cell Lung Cancer
Cancer Res., December 1, 2002; 62(23): 7124 - 7129.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. R. Collingridge, V. A. Carroll, M. Glaser, E. O. Aboagye, S. Osman, O. C. Hutchinson, H. Barthel, S. K. Luthra, F. Brady, R. Bicknell, et al.
The Development of [124I]Iodinated-VG76e: A Novel Tracer for Imaging Vascular Endothelial Growth Factor in Vivo Using Positron Emission Tomography
Cancer Res., October 15, 2002; 62(20): 5912 - 5919.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. F. Schoppmann, P. Birner, J. Stockl, R. Kalt, R. Ullrich, C. Caucig, E. Kriehuber, K. Nagy, K. Alitalo, and D. Kerjaschki
Tumor-Associated Macrophages Express Lymphatic Endothelial Growth Factors and Are Related to Peritumoral Lymphangiogenesis
Am. J. Pathol., September 1, 2002; 161(3): 947 - 956.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
I. B. Lobov, P. C. Brooks, and R. A. Lang
From the Cover: Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo
PNAS, August 20, 2002; 99(17): 11205 - 11210.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
R. K. Jain and B. T. Fenton
Intratumoral Lymphatic Vessels: A Case of Mistaken Identity or Malfunction?
J Natl Cancer Inst, March 20, 2002; 94(6): 417 - 421.
[Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. E. Crawford, V. Stellmach, M. Ranalli, X. Huang, L. Huang, O. Volpert, G. H. De Vries, L. P. Abramson, and N. Bouck
Pigment epithelium-derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity
J. Cell Sci., March 14, 2002; 114(24): 4421 - 4428.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Eggert, M. A. Grotzer, N. Ikegaki, X.-g. Liu, A. E. Evans, and G. M. Brodeur
Expression of the Neurotrophin Receptor TrkA Down-Regulates Expression and Function of Angiogenic Stimulators in SH-SY5Y Neuroblastoma Cells
Cancer Res., March 1, 2002; 62(6): 1802 - 1808.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y.-Q. Huang, J.-J. Li, L. Hu, M. Lee, and S. Karpatkin
Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells
Blood, March 1, 2002; 99(5): 1646 - 1650.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
I. HARTLAPP, R. ABE, R. W. SAEED, T. PENG, W. VOELTER, R. BUCALA, and C. N. METZ
Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo
FASEB J, October 1, 2001; 15(12): 2215 - 2224.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. S. Kerbel
Clinical Trials of Antiangiogenic Drugs: Opportunities, Problems, and Assessment of Initial Results
J. Clin. Oncol., September 15, 2001; 19(90001): 45s - 51.
[Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Skobe, L. M. Hamberg, T. Hawighorst, M. Schirner, G. L. Wolf, K. Alitalo, and M. Detmar
Concurrent Induction of Lymphangiogenesis, Angiogenesis, and Macrophage Recruitment by Vascular Endothelial Growth Factor-C in Melanoma
Am. J. Pathol., September 1, 2001; 159(3): 893 - 903.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Shusterman, S. A. Grupp, R. Barr, D. Carpentieri, H. Zhao, and J. M. Maris
The Angiogenesis Inhibitor TNP-470 Effectively Inhibits Human Neuroblastoma Xenograft Growth, Especially in the Setting of Subclinical Disease
Clin. Cancer Res., April 1, 2001; 7(4): 977 - 984.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2000 by the American Association for Cancer Research.