| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
1 Department of Otolaryngology, University of Pittsburgh Medical Center; 2 Department of Pharmacology, University of Pittsburgh Cancer Institute; 3 Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania; and 4 Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado
Requests for reprints: Jennifer Rubin Grandis, Department of Otolaryngology, University of Pittsburgh Medical Center, 203 Lothrop Street, Suite 500, Pittsburgh, PA 15213. Phone: 412-647-5250; Fax: 412-647-0108; E-mail: jgrandis{at}pitt.edu.
G protein–coupled receptors (GPCR) and the epidermal growth factor receptor (EGFR) are often both overexpressed and contribute to the growth of cancers by activating autocrine pathways. GPCR ligands have been reported to trigger EGFR signaling via receptor cross-talk in cancer cells. Here, we show that GPCR ligands prostaglandin E2 (PGE2) and bradykinin (BK) activate EGFR signaling. Inhibition of EGFR using several strategies, including small-molecule inhibitors and an EGFR-specific antibody, resulted in partial attenuation of signaling downstream of EGFR. PGE2 and BK triggered EGFR signaling by increasing selective autocrine release of transforming growth factor-
(TGF-). Inhibition of tumor necrosis factor-–converting enzyme abrogated BK- or PGE2-mediated activation of EGFR signaling. Both PGE2 and BK stimulated head and neck squamous cell carcinoma (HNSCC) invasion via EGFR. Treatment of HNSCC cells with the BK antagonist CU201 resulted in growth inhibition. The combination of CU201 with the EGFR small-molecule inhibitor erlotinib resulted in additive inhibitory effects on HNSCC cell growth in vitro. Inhibition of the PGE2 synthesis pathway with sulindac induced HNSCC cytotoxicity at high doses (EC50, 620 µmol/L). However, combined inhibition of both EGFR with the tyrosine kinase inhibitor erlotinib and GPCR with sulindac at low doses of 6 and 310 µmol/L, respectively, resulted in synergistic killing of HNSCC tumor cells. Combined blockade of both EGFR and GPCRs may be a rational strategy to treat cancers, including HNSCC that shows cross-talk between GPCR and EGFR signaling pathways. (Cancer Res 2006; 66(24): 11831-9)
This article has been cited by other articles:
|
|
 |
|
  P. Arun, M. S. Brown, R. Ehsanian, Z. Chen, and C. Van Waes Nuclear NF-{kappa}B p65 Phosphorylation at Serine 276 by Protein Kinase A Contributes to the Malignant Phenotype of Head and Neck Cancer Clin. Cancer Res., October 1, 2009; 15(19): 5974 - 5984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-C. Liu, Y.-M. Jen, S. S. Jiang, J.-L. Chang, C. A. Hsiung, C.-H. Wang, and J.-L. Juang G{alpha}12-Mediated Pathway Promotes Invasiveness of Nasopharyngeal Carcinoma by Modulating Actin Cytoskeleton Reorganization Cancer Res., August 1, 2009; 69(15): 6122 - 6130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, C. D. MacCalman, Y.-l. Wang, and P. C. K. Leung Promotion of Human Trophoblasts Invasion by Gonadotropin-Releasing Hormone (GnRH) I and GnRH II via Distinct Signaling Pathways Mol. Endocrinol., July 1, 2009; 23(7): 1014 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, J. D. Ritzenthaler, X. Sun, J. Roman, and S. Han Prostaglandin E2 Stimulates Human Lung Carcinoma Cell Growth through Induction of Integrin-Linked Kinase: The Involvement of EP4 and Sp1 Cancer Res., February 1, 2009; 69(3): 896 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang, N. Bhola, S. Kalyankrishna, W. Gooding, J. Hunt, R. Seethala, J. R. Grandis, and J. M. Siegfried Kinin B2 Receptor Mediates Induction of Cyclooxygenase-2 and Is Overexpressed in Head and Neck Squamous Cell Carcinomas Mol. Cancer Res., December 1, 2008; 6(12): 1946 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Misawa, Y. Ueda, T. Kanazawa, Y. Misawa, I. Jang, J. C. Brenner, T. Ogawa, S. Takebayashi, R. A. Grenman, J. G. Herman, et al. Epigenetic Inactivation of Galanin Receptor 1 in Head and Neck Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7604 - 7613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lehnerdt, P. Franz, A. Bankfalvi, S. Grehl, K. Jahnke, S. Lang, K. W. Schmid, W. Siffert, and U. H. Frey Association Study of the G-Protein {beta}3 Subunit C825T Polymorphism with Disease Progression an Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 3203 - 3207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jain, G. Chakraborty, R. Raja, S. Kale, and G. C. Kundu Prostaglandin E2 Regulates Tumor Angiogenesis in Prostate Cancer Cancer Res., October 1, 2008; 68(19): 7750 - 7759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yan, H. Zou, F. Tian, J. R. Grandis, A. J. Mixson, P. Y. Lu, and L.-Y. Li Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth Mol. Cancer Ther., June 1, 2008; 7(6): 1355 - 1364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hallman, S. Zhuang, and R. G. Schnellmann Regulation of Dedifferentiation and Redifferentiation in Renal Proximal Tubular Cells by the Epidermal Growth Factor Receptor J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 520 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Seethala, W. E. Gooding, P. N. Handler, B. Collins, Q. Zhang, J. M. Siegfried, and J. R. Grandis Immunohistochemical Analysis of Phosphotyrosine Signal Transducer and Activator of Transcription 3 and Epidermal Growth Factor Receptor Autocrine Signaling Pathways in Head and Neck Cancers and Metastatic Lymph Nodes Clin. Cancer Res., March 1, 2008; 14(5): 1303 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Bawolak, L. Gera, G. Morissette, J. M. Stewart, and F. Marceau B-9972 (D-Arg-[Hyp3,Igl5,Oic7,Igl8]-bradykinin) Is an Inactivation-Resistant Agonist of the Bradykinin B2 Receptor Derived from the Peptide Antagonist B-9430 (D-Arg-[Hyp3,Igl5,D-Igl7,Oic8]-bradykinin): Pharmacologic Profile and Effective Induction of Receptor Degradation J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 534 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Siegfried, C. T. Gubish, M. E. Rothstein, P. E. Q. de Oliveira, and L. P. Stabile Signaling Pathways Involved in Cyclooxygenase-2 Induction by Hepatocyte Growth Factor in Non Small-Cell Lung Cancer Mol. Pharmacol., September 1, 2007; 72(3): 769 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Donnini, F. Finetti, R. Solito, E. Terzuoli, A. Sacchetti, L. Morbidelli, P. Patrignani, and M. Ziche EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways FASEB J, August 1, 2007; 21(10): 2418 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Karamouzis, J. R. Grandis, and A. Argiris Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas JAMA, July 4, 2007; 298(1): 70 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Karamouzis, P. Konstantinopoulos, and A. Papavassiliou Intriguing issues of EGFR targeting in head and neck cancer Ann. Onc., May 1, 2007; 18(5): 962 - 962. [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 |
