| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
The purpose of this study was to determine whether the expression of epidermal growth factor receptor (EGF-R) and activated EGF-R by tumor-associated endothelial cells is influenced by interaction with specific growth factors in the microenvironment. Different human carcinoma cell lines expressing EGF-R with low or high levels of EGF/transforming growth factor (TGF)-
were implanted into orthotopic organs of nude mice. In the EGF/TGF--positive bladder cancer (253J-BV), pancreatic cancer (L3.6pl), and renal cancer (RBM1-IT) but not in the EGF/TGF--negative renal cancer SN12-PM6, tumor-associated endothelial cells expressed EGF-R and activated EGF-R. Mice were implanted with human 253J-BV bladder tumors (EGF+) or human SN12-PM6 renal tumors (EGF-). Treatment with oral PKI 166 (a specific inhibitor of EGF-R phosphorylation) alone, intraperitoneal paclitaxel alone (253J-BV), gemcitabine alone (SN12-PM6), or combination of PKI 166 and chemotherapy produced a 60%, 32%, or 81% reduction in the volume of 253J-BV bladder tumors, respectively, and 26%, 23%, or 51% reduction in the volume of SN12-PM6 kidney tumors, respectively. Immunohistochemical analyses demonstrated down-regulation of activated EGF-R in EGF/TGF--positive and EGF/TGF--negative lesions from mice treated with PKI 166, although apoptosis of tumor-associated endothelial cells was found only in EGF/TGF--positive tumors. Collectively, these data suggest that expression of activated EGF-R by tumor-associated endothelial cells provides an important target for therapy.
This article has been cited by other articles:
 |
|
 |
|
  K. Al-Nedawi, B. Meehan, R. S. Kerbel, A. C. Allison, and J. Rak Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR PNAS, March 10, 2009; 106(10): 3794 - 3799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Bradshaw-Pierce, C. A. Steinhauer, D. Raben, and D. L. Gustafson Pharmacokinetic-directed dosing of vandetanib and docetaxel in a mouse model of human squamous cell carcinoma Mol. Cancer Ther., September 1, 2008; 7(9): 3006 - 3017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sasaki, T. Nakamura, R. B. Rebhun, H. Cheng, K. S. Hale, R. Z. Tsan, I. J. Fidler, and R. R. Langley Modification of the Primary Tumor Microenvironment by Transforming Growth Factor {alpha}-Epidermal Growth Factor Receptor Signaling Promotes Metastasis in an Orthotopic Colon Cancer Model Am. J. Pathol., July 1, 2008; 173(1): 205 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Shen, Z. F. Yang, Y. Gao, J. C. Li, H. X. Chen, C. C. Liu, R. T.P. Poon, S. T. Fan, J. M. Luk, K. H. Sze, et al. The Kringle 1 Domain of Hepatocyte Growth Factor Has Antiangiogenic and Antitumor Cell Effects on Hepatocellular Carcinoma Cancer Res., January 15, 2008; 68(2): 404 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
W. Wu, M. S. O'Reilly, R. R. Langley, R. Z. Tsan, C. H. Baker, N. Bekele, X. M. Tang, A. Onn, I. J. Fidler, and R. S. Herbst Expression of epidermal growth factor (EGF)/transforming growth factor-{alpha} by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice Mol. Cancer Ther., October 1, 2007; 6(10): 2652 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lu, A. A. Kamat, Y. G. Lin, W. M. Merritt, C. N. Landen, T. J. Kim, W. Spannuth, T. Arumugam, L. Y. Han, N. B. Jennings, et al. Dual Targeting of Endothelial Cells and Pericytes in Antivascular Therapy for Ovarian Carcinoma Clin. Cancer Res., July 15, 2007; 13(14): 4209 - 4217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Langley and I. J. Fidler Tumor Cell-Organ Microenvironment Interactions in the Pathogenesis of Cancer Metastasis Endocr. Rev., May 1, 2007; 28(3): 297 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wu, A. Onn, T. Isobe, S. Itasaka, R. R. Langley, T. Shitani, K. Shibuya, R. Komaki, A. J. Ryan, I. J. Fidler, et al. Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade Mol. Cancer Ther., February 1, 2007; 6(2): 471 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. Xu, D. M. Cochran, R. T. Tong, F. Winkler, S. Kashiwagi, R. K. Jain, and D. Fukumura Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models. Cancer Res., April 15, 2006; 66(8): 3971 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Pino, M. Shrader, C. H. Baker, F. Cognetti, H. Q. Xiong, J. L. Abbruzzese, and D. J. McConkey Transforming Growth Factor {alpha} Expression Drives Constitutive Epidermal Growth Factor Receptor Pathway Activation and Sensitivity to Gefitinib (Iressa) in Human Pancreatic Cancer Cell Lines. Cancer Res., April 1, 2006; 66(7): 3802 - 3812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. P. Milling Smith, S. Battersby, K. J. Sales, H. O. D. Critchley, and H. N. Jabbour Prostacyclin Receptor Up-Regulates the Expression of Angiogenic Genes in Human Endometrium via Cross Talk with Epidermal Growth Factor Receptor and the Extracellular Signaling Receptor Kinase 1/2 Pathway Endocrinology, April 1, 2006; 147(4): 1697 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Amin, K. Hida, D. R. Bielenberg, and M. Klagsbrun Tumor Endothelial Cells Express Epidermal Growth Factor Receptor (EGFR) but not ErbB3 and Are Responsive to EGF and to EGFR Kinase Inhibitors Cancer Res., February 15, 2006; 66(4): 2173 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yano, H. Muguruma, Y. Matsumori, H. Goto, E. Nakataki, N. Edakuni, H. Tomimoto, S. Kakiuchi, A. Yamamoto, H. Uehara, et al. Antitumor Vascular Strategy for Controlling Experimental Metastatic Spread of Human Small-Cell Lung Cancer Cells with ZD6474 in Natural Killer Cell-Depleted Severe Combined Immunodeficient Mice Clin. Cancer Res., December 15, 2005; 11(24): 8789 - 8798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, J. F. Wang, B. Chandran, K. Persaud, B. Pytowski, J. Fingeroth, and J. E. Groopman Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection J. Biol. Chem., July 15, 2005; 280(28): 26216 - 26224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Sini, L. Wyder, C. Schnell, T. O'Reilly, A. Littlewood, R. Brandt, N. E. Hynes, and J. Wood The Antitumor and Antiangiogenic Activity of Vascular Endothelial Growth Factor Receptor Inhibition Is Potentiated by ErbB1 Blockade Clin. Cancer Res., June 15, 2005; 11(12): 4521 - 4532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. C. Lev, S. J. Kim, A. Onn, V. Stone, D.-H. Nam, S. Yazici, I. J. Fidler, and J. E. Price Inhibition of Platelet-Derived Growth Factor Receptor Signaling Restricts the Growth of Human Breast Cancer in the Bone of Nude Mice Clin. Cancer Res., January 1, 2005; 11(1): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. Onn, A. M. Correa, M. Gilcrease, T. Isobe, E. Massarelli, C. D. Bucana, M. S. O'Reilly, W. K. Hong, I. J. Fidler, J. B. Putnam, et al. Synchronous Overexpression of Epidermal Growth Factor Receptor and HER2-neu Protein Is a Predictor of Poor Outcome in Patients with Stage I Non-Small Cell Lung Cancer Clin. Cancer Res., January 1, 2004; 10(1): 136 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Weber, M. Doucet, J. E. Price, C. Baker, S. J. Kim, and I. J. Fidler Blockade of Epidermal Growth Factor Receptor Signaling Leads to Inhibition of Renal Cell Carcinoma Growth in the Bone of Nude Mice Cancer Res., June 1, 2003; 63(11): 2940 - 2947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, H. Uehara, T. Karashima, D. L. Shepherd, J. J. Killion, and I. J. Fidler 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 Mice Clin. Cancer Res., March 1, 2003; 9(3): 1200 - 1210. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
