| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology Section, Pediatric Branch [T. K., L. J. H.], Department of Pathology [M. T.], National Cancer Institute, Building 10/13N240, Bethesda, Maryland 20892-1928
In a previous study, we have shown that insulin-like growth factor type 2 (IGF-2) functions as an autocrine growth factor in human rhabdomyosarcoma (RMS) cell lines. In addition, we demonstrated that the inhibition of binding of IGF-2 to the IGF-1 receptor, mediated by suramin, blocked the growth of RMS cells in vitro. We now report that, in vivo, a specific IGF-1 receptor blocking antibody (
IR-3), but not suramin, suppresses RMS tumor growth. Both progression of tumor growth in tumor-bearing animals and formation of newly established tumors were suppressed by treatment with IR-3. Histological analysis of tumors from treated animals did not reveal necrotic lesions, implying that the treatments had no cytotoxic effect. The decrease in tumor growth was associated with a decrease of p34cdc2, a cellular protein involved in cell cycle regulation, suggesting that treatment resulted in the arrest of cellular proliferation. We speculate, therefore, that agents which block the IGF signaling pathway may find application in treatment of RMS.
1 To whom requests for reprints should be addressed, at Molecular Oncology Section, Pediatric Branch, National Cancer Institute, Building 10/13N240, Bethesda, MD 20892-1928.
Received 8/19/94. Accepted 9/14/94.
This article has been cited by other articles:
|
|
 |
|
  L. Cao, Y. Yu, I. Darko, D. Currier, L. H. Mayeenuddin, X. Wan, C. Khanna, and L. J. Helman Addiction to Elevated Insulin-like Growth Factor I Receptor and Initial Modulation of the AKT Pathway Define the Responsiveness of Rhabdomyosarcoma to the Targeting Antibody Cancer Res., October 1, 2008; 68(19): 8039 - 8048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Rowinsky, H. Youssoufian, J. R. Tonra, P. Solomon, D. Burtrum, and D. L. Ludwig IMC-A12, a Human IgG1 Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor Clin. Cancer Res., September 15, 2007; 13(18): 5549s - 5555s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. T. Kurmasheva, F. C. Harwood, and P. J. Houghton Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors Mol. Cancer Ther., May 1, 2007; 6(5): 1620 - 1628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sachdev and D. Yee Disrupting insulin-like growth factor signaling as a potential cancer therapy Mol. Cancer Ther., January 1, 2007; 6(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Martin, N. Melnyk, M. Pollard, M. Bowden, H. Leong, T. J. Podor, M. Gleave, and P. H. B. Sorensen The Insulin-Like Growth Factor I Receptor Is Required for Akt Activation and Suppression of Anoikis in Cells Transformed by the ETV6-NTRK3 Chimeric Tyrosine Kinase. Mol. Cell. Biol., March 1, 2006; 26(5): 1754 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Stromberg, S. Ekman, L. Girnita, L. Y. Dimberg, O. Larsson, M. Axelson, J. Lennartsson, U. Hellman, K. Carlson, A. Osterborg, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells Blood, January 15, 2006; 107(2): 669 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nabarro, N. Himoudi, A. Papanastasiou, K. Gilmour, S. Gibson, N. Sebire, A. Thrasher, M. P. Blundell, M. Hubank, G. Canderan, et al. Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein J. Exp. Med., November 21, 2005; 202(10): 1399 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Scotlandi, M. C. Manara, G. Nicoletti, P.-L. Lollini, S. Lukas, S. Benini, S. Croci, S. Perdichizzi, D. Zambelli, M. Serra, et al. Antitumor Activity of the Insulin-Like Growth Factor-I Receptor Kinase Inhibitor NVP-AEW541 in Musculoskeletal Tumors Cancer Res., May 1, 2005; 65(9): 3868 - 3876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Cohen, D. A. Baker, C. Soderstrom, G. Tkalcevic, A. M. Rossi, P. E. Miller, M. W. Tengowski, F. Wang, A. Gualberto, J. S. Beebe, et al. Combination Therapy Enhances the Inhibition of Tumor Growth with the Fully Human Anti-Type 1 Insulin-Like Growth Factor Receptor Monoclonal Antibody CP-751,871 Clin. Cancer Res., March 1, 2005; 11(5): 2063 - 2073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Burtrum, Z. Zhu, D. Lu, D. M. Anderson, M. Prewett, D. S. Pereira, R. Bassi, R. Abdullah, A. T. Hooper, H. Koo, et al. A Fully Human Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor Blocks Ligand-Dependent Signaling and Inhibits Human Tumor Growth in Vivo Cancer Res., December 15, 2003; 63(24): 8912 - 8921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Maloney, J. L. McLaughlin, N. E. Dagdigian, L. M. Garrett, K. M. Connors, X.-M. Zhou, W. A. Blattler, T. Chittenden, and R. Singh An Anti-Insulin-like Growth Factor I Receptor Antibody That Is a Potent Inhibitor of Cancer Cell Proliferation Cancer Res., August 15, 2003; 63(16): 5073 - 5083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Hassan and V. M. Macaulay The insulin-like growth factor system as a therapeutic target in colorectal cancer Ann. Onc., March 1, 2002; 13(3): 349 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. All-Ericsson, L. Girnita, S. Seregard, A. Bartolazzi, M. J. Jager, and O. Larsson Insulin-like Growth Factor-1 Receptor in Uveal Melanoma: A Predictor for Metastatic Disease and a Potential Therapeutic Target Invest. Ophthalmol. Vis. Sci., January 1, 2002; 43(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Reiss, X. Tu, G. Romano, F. Peruzzi, J. Y. Wang, and R. Baserga Intracellular Association of a Mutant Insulin-like Growth Factor Receptor with Endogenous Receptors Clin. Cancer Res., July 1, 2001; 7(7): 2134 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Benini, M. C. Manara, N. Baldini, V. Cerisano, Massimo Serra, M. Mercuri, P.-L. Lollini, P. Nanni, P. Picci, and K. Scotlandi Inhibition of Insulin-like Growth Factor I Receptor Increases the Antitumor Activity of Doxorubicin and Vincristine against Ewing's Sarcoma Cells Clin. Cancer Res., June 1, 2001; 7(6): 1790 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Datta, C. Sundberg, S. A. Karumanchi, and D. Mukhopadhyay The 104-123 Amino Acid Sequence of the {beta}-domain of von Hippel-Lindau Gene Product Is Sufficient to Inhibit Renal Tumor Growth and Invasion Cancer Res., March 1, 2001; 61(5): 1768 - 1775. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. LeRoith Insulin-like Growth Factors in Pediatric Health and Disease J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4355 - 4361. [Full Text]
|
|
|
|
|
|
J. A. Toretsky, M. Thakar, A. E. Eskenazi, and C. N. Frantz Phosphoinositide 3-Hydroxide Kinase Blockade Enhances Apoptosis in the Ewing's Sarcoma Family of Tumors Cancer Res., November 1, 1999; 59(22): 5745 - 5750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Manes, M. Llorente, R. A. Lacalle, C. Gomez-Mouton, L. Kremer, E. Mira, and C. Martinez-A The Matrix Metalloproteinase-9 Regulates the Insulin-like Growth Factor-triggered Autocrine Response in DU-145 Carcinoma Cells J. Biol. Chem., March 12, 1999; 274(11): 6935 - 6945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dagher and L. Helman Rhabdomyosarcoma: An Overview Oncologist, February 1, 1999; 4(1): 34 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
W. Li, Y.-X. Jiang, J. Zhang, L. Soon, L. Flechner, V. Kapoor, J. H. Pierce, and L.-H. Wang Protein Kinase C-delta Is an Important Signaling Molecule in Insulin-Like Growth Factor I Receptor-Mediated Cell Transformation Mol. Cell. Biol., October 1, 1998; 18(10): 5888 - 5898. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Niebauer, C.-D. Pflaum, A. L. Clark, C. J. Strasburger, J. Hooper, P. A. Poole-Wilson, A. J. S. Coats, and S. D. Anker Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation J. Am. Coll. Cardiol., August 1, 1998; 32(2): 393 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Blakesley, A. P. Koval, B. S. Stannard, A. Scrimgeour, and D. LeRoith Replacement of Tyrosine 1251 in the Carboxyl Terminus of the Insulin-like Growth Factor-I Receptor Disrupts the Actin Cytoskeleton and Inhibits Proliferation and Anchorage-independent Growth J. Biol. Chem., July 17, 1998; 273(29): 18411 - 18422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Toretsky, T. Kalebic, V. Blakesley, D. LeRoith, and L. J. Helman The Insulin-like Growth Factor-I Receptor Is Required for EWS/FLI-1 Transformation of Fibroblasts J. Biol. Chem., December 5, 1997; 272(49): 30822 - 30827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Rininsland, T. R. Johnson, C. L. Chernicky, E. Schulze, P. Burfeind, J. Ilan, and J. Ilan Suppression of insulin-like growth factor type I receptor by a triple-helix strategy inhibits IGF-I transcription and tumorigenic potential of rat C6 glioblastoma cells PNAS, May 27, 1997; 94(11): 5854 - 5859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. M. Li, D. H. Schacher, Q. Liu, S. Arkins, N. Rebeiz, R. H. McCusker Jr., R. Dantzer, and K. W. Kelley Regulation of Myeloid Growth and Differentiation by the Insulin-Like Growth Factor I Receptor Endocrinology, January 1, 1997; 138(1): 362 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Smith, J. Abrams, E. L. Trimble, and R. S. Ungerleider Dose Intensity of Chemotherapy for Childhood Cancers Oncologist, October 1, 1996; 1(5): 293 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, M. Resnicoff, and R. Baserga Effect of Mutations at Serines 1280-1283 on the Mitogenic and Transforming Activities of the Insulin-like Growth Factor I Receptor J. Biol. Chem., May 24, 1996; 271(21): 12254 - 12260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Miura, E. Surmacz, J.-L. Burgaud, and R. Baserga Different Effects on Mitogenesis and Transformation of a Mutation at Tyrosine 1251 of the Insulin-like Growth Factor I Receptor J. Biol. Chem., September 22, 1995; 270(38): 22639 - 22644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sachdev, Y.-X. Jiang, W. Li, T. Miki, H. Maruta, M. S. A. Nur-e-Kamal, and L.-H. Wang Differential Requirement for Rho Family GTPases in an Oncogenic Insulin-like Growth Factor-I Receptor-induced Cell Transformation J. Biol. Chem., July 6, 2001; 276(28): 26461 - 26471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Datta, R. Nambudripad, S. Pal, M. Zhou, H. T. Cohen, and D. Mukhopadhyay Inhibition of Insulin-like Growth Factor-I-mediated Cell Signaling by the von Hippel-Lindau Gene Product in Renal Cancer J. Biol. Chem., June 30, 2000; 275(27): 20700 - 20706. [Abstract] [Full Text] [PDF]
|
|
| 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 |
