Clinical Cancer Research CR Surrogrates Advances in Breast Cancer
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 Kim, S.-J.
Right arrow Articles by Fidler, I. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, S.-J.
Right arrow Articles by Fidler, I. J.
Clinical Cancer Research Vol. 9, 1200-1210, March 2003
© 2003 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

Blockade of Epidermal Growth Factor Receptor Signaling in Tumor Cells and Tumor-associated Endothelial Cells for Therapy of Androgen-independent Human Prostate Cancer Growing in the Bone of Nude Mice1

Sun-Jin Kim2, Hisanori Uehara2, Takashi Karashima, David L. Shepherd, Jerald J. Killion and Isaiah J. Fidler3

Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Purpose: We determined whether blockade of the epidermal growth factor receptor (EGF-R) signaling pathway by oral administration of the EGF-R tyrosine kinase inhibitor (PKI 166) alone or in combination with injectable Taxol inhibits the growth of PC-3MM2 human prostate cancer cells in the bone of nude mice.

Experimental Design: Male nude mice implanted with PC-3MM2 cells in the tibia were treated with oral administrations of PKI 166 or PKI 166 plus injectable Taxol beginning 3 days after implantation. The incidence and size of bone tumors and destruction of bone were determined by digitalized radiography. Expression of epidermal growth factor (EGF), EGF-R, and activated EGF-R in tumor cells and tumor-associated endothelial cells was determined by immunohistochemistry.

Results: Oral administration of PKI 166 or PKI 166 plus injectable Taxol reduced the incidence and size of bone tumors and destruction of bone. Immunohistochemical analysis revealed that PC-3MM2 cells growing adjacent to the bone expressed high levels of EGF and activated EGF-R, whereas tumor cells in the adjacent musculature did not. Moreover, endothelial cells within the bone tumor lesions, but not in uninvolved bone or tumors in the muscle, expressed high levels of activated EGF-R. Treatment with PKI 166 and more so with PKI 166 plus Taxol significantly inhibited phosphorylation of EGF-R on tumor and endothelial cells and induced significant apoptosis and endothelial cells within tumor lesions.

Conclusions: These data indicate that endothelial cells exposed to EGF produced by tumor cells express activated EGF-R and that targeting EGF-R can produce significant therapeutic effects against prostate cancer bone metastasis.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. I. Park, J. Zhang, K. A. Phillips, J. C. Araujo, A. M. Najjar, A. Y. Volgin, J. G. Gelovani, S.-J. Kim, Z. Wang, and G. E. Gallick
Targeting Src Family Kinases Inhibits Growth and Lymph Node Metastases of Prostate Cancer in an Orthotopic Nude Mouse Model
Cancer Res., May 1, 2008; 68(9): 3323 - 3333.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
L. A Kingsley, P. G J Fournier, J. M Chirgwin, and T. A Guise
Molecular Biology of Bone Metastasis
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 443 - 457.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra
Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies
Endocr. Rev., April 1, 2008; 29(2): 234 - 252.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
N. Normanno and A. De Luca
Erlotinib in Pancreatic Cancer: Are Tumor Cells the (only) Target?
J. Clin. Oncol., December 20, 2007; 25(36): 5836 - 5837.
[Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. A. Kingsley, P. G.J. Fournier, J. M. Chirgwin, and T. A. Guise
Molecular Biology of Bone Metastasis
Mol. Cancer Ther., October 1, 2007; 6(10): 2609 - 2617.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Sandler
Bevacizumab in Non Small Cell Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4613s - 4616s.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. O. Hanrahan and J. V. Heymach
Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Vandetanib (ZD6474) and AZD2171 in Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4617s - 4622s.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
J. Tabernero
The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents
Mol. Cancer Res., March 1, 2007; 5(3): 203 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Mimeault, S. L. Johansson, G. Vankatraman, E. Moore, J.-P. Henichart, P. Depreux, M.-F. Lin, and S. K. Batra
Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells
Mol. Cancer Ther., March 1, 2007; 6(3): 967 - 978.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Bandyopadhyay, Y. Wang, R. Zhan, S. K. Pai, M. Watabe, M. Iiizumi, E. Furuta, S. Mohinta, W. Liu, S. Hirota, et al.
The Tumor Metastasis Suppressor Gene Drg-1 Down-regulates the Expression of Activating Transcription Factor 3 in Prostate Cancer
Cancer Res., December 15, 2006; 66(24): 11983 - 11990.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Ono and M. Kuwano
Molecular Mechanisms of Epidermal Growth Factor Receptor (EGFR) Activation and Response to Gefitinib and Other EGFR-Targeting Drugs
Clin. Cancer Res., December 15, 2006; 12(24): 7242 - 7251.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
Y. Kitadai, T. Sasaki, T. Kuwai, T. Nakamura, C. D. Bucana, and I. J. Fidler
Targeting the Expression of Platelet-Derived Growth Factor Receptor by Reactive Stroma Inhibits Growth and Metastasis of Human Colon Carcinoma
Am. J. Pathol., December 1, 2006; 169(6): 2054 - 2065.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Sandler and R. Herbst
Combining targeted agents: blocking the epidermal growth factor and vascular endothelial growth factor pathways.
Clin. Cancer Res., July 15, 2006; 12(14): 4421s - 4425s.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S.-J. Kim, H. Uehara, S. Yazici, J. E. Busby, T. Nakamura, J. He, M. Maya, C. Logothetis, P. Mathew, X. Wang, et al.
Targeting platelet-derived growth factor receptor on endothelial cells of multidrug-resistant prostate cancer.
J Natl Cancer Inst, June 7, 2006; 98(11): 783 - 793.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
N. Normanno and W. J Gullick
Epidermal growth factor receptor tyrosine kinase inhibitors and bone metastases: different mechanisms of action for a novel therapeutic application?
Endocr. Relat. Cancer, March 1, 2006; 13(1): 3 - 6.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
A. Angelucci, G. L. Gravina, N. Rucci, D. Millimaggi, C. Festuccia, P. Muzi, A. Teti, C. Vicentini, and M. Bologna
Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice.
Endocr. Relat. Cancer, March 1, 2006; 13(1): 197 - 210.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. D. Loberg, C. J. Logothetis, E. T. Keller, and K. J. Pienta
Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype
J. Clin. Oncol., November 10, 2005; 23(32): 8232 - 8241.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. H. Thaker, S. Yazici, M. B. Nilsson, K. Yokoi, R. Z. Tsan, J. He, S.-J. Kim, I. J. Fidler, and A. K. Sood
Antivascular Therapy for Orthotopic Human Ovarian Carcinoma through Blockade of the Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptors
Clin. Cancer Res., July 1, 2005; 11(13): 4923 - 4933.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. N. Younes, O. G. Yigitbasi, Y. W. Park, S.-J. Kim, S. A. Jasser, V. S. Hawthorne, Y. D. Yazici, M. Mandal, B. N. Bekele, C. D. Bucana, et al.
Antivascular Therapy of Human Follicular Thyroid Cancer Experimental Bone Metastasis by Blockade of Epidermal Growth Factor Receptor and Vascular Growth Factor Receptor Phosphorylation
Cancer Res., June 1, 2005; 65(11): 4716 - 4727.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S.-J. Kim, H. Uehara, S. Yazici, J. He, R. R. Langley, P. Mathew, D. Fan, and I. J. Fidler
Modulation of Bone Microenvironment with Zoledronate Enhances the Therapeutic Effects of STI571 and Paclitaxel against Experimental Bone Metastasis of Human Prostate Cancer
Cancer Res., May 1, 2005; 65(9): 3707 - 3715.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Yokoi, P. H. Thaker, S. Yazici, R. R. Rebhun, D.-H. Nam, J. He, S.-J. Kim, J. L. Abbruzzese, S. R. Hamilton, and I. J. Fidler
Dual Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation by AEE788 Reduces Growth and Metastasis of Human Colon Carcinoma in an Orthotopic Nude Mouse Model
Cancer Res., May 1, 2005; 65(9): 3716 - 3725.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. S. Herbst, D. H. Johnson, E. Mininberg, D. P. Carbone, T. Henderson, E. S. Kim, G. Blumenschein Jr, J. J. Lee, D. D. Liu, M. T. Truong, et al.
Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non-Small-Cell Lung Cancer
J. Clin. Oncol., April 10, 2005; 23(11): 2544 - 2555.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. W. Park, M. N. Younes, S. A. Jasser, O. G. Yigitbasi, G. Zhou, C. D. Bucana, B. N. Bekele, and J. N. Myers
AEE788, a Dual Tyrosine Kinase Receptor Inhibitor, Induces Endothelial Cell Apoptosis in Human Cutaneous Squamous Cell Carcinoma Xenografts in Nude Mice
Clin. Cancer Res., March 1, 2005; 11(5): 1963 - 1973.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. Gasparini, R. Longo, M. Fanelli, and B. A. Teicher
Combination of Antiangiogenic Therapy With Other Anticancer Therapies: Results, Challenges, and Open Questions
J. Clin. Oncol., February 20, 2005; 23(6): 1295 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Onn, T. Isobe, W. Wu, S. Itasaka, T. Shintani, K. Shibuya, Y. Kenji, M. S. O'Reilly, I. J. Fidler, and R. S. Herbst
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer
Clin. Cancer Res., December 15, 2004; 10(24): 8613 - 8619.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. J. Kim, H. Uehara, S. Yazici, R. R. Langley, J. He, R. Tsan, D. Fan, J. J. Killion, and I. J. Fidler
Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice
Cancer Res., June 15, 2004; 64(12): 4201 - 4208.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. M. Apte, D. Fan, J. J. Killion, and I. J. Fidler
Targeting the Platelet-Derived Growth Factor Receptor in Antivascular Therapy for Human Ovarian Carcinoma
Clin. Cancer Res., February 1, 2004; 10(3): 897 - 908.
[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
Copyright © 2003 by the American Association for Cancer Research.