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Received on September 2, 2003
Accepted on December 19, 2003
Molecular Diagnostics and Genetics |
1 Department of Dermatology
2 Institute for Clinical Chemistry
3 Institute of Pathology
4 Department of Neurology, University of Regensburg, Regensburg, Germany
* To whom correspondence should be addressed. E-mail: thomas.vogt{at}klinik.uni-regensburg.de.
Background: Eph receptors and their ligands, the ephrins, represent a large class of cell-cell communication molecules with well-defined developmental functions. Their role in healthy adult tissues and in human disease is still largely unknown, although diverse roles in carcinogenesis have been postulated.
Methods: We established a set of fluorescent PCR probes and primers for the definition of individual gene expression profiles of 12 different Eph receptors and 8 ephrins in 13 different healthy tissues. The mRNA expression profiles were studied in human lung, colorectal, kidney, liver, and brain cancers.
Results: The family of Eph receptors/ephrins was widely expressed in adult tissues with organ-site-specific patterns: EphB6 expression was highest in the thymus, compatible with an involvement in T-cell maturation. Brain and testis shared a unique pattern with EphA6, EphA8, and EphB1 being the most prominent. EphA7 had a high abundance in the kidney vasculature. Ephrin-A3 was up-regulated 26-fold in lung cancer, and EphB2 was up-regulated 9-fold in hepatocellular carcinoma. EphA8 was down-regulated in colon cancer, and EphA1/EphA8 was down-regulated in glioblastomas.
Conclusion: Eph/Ephrins are widely expressed in all adult organs with certain organ-site-specific patterns. Because their function in adult tissues remains unknown, further analysis of their role in disease may disclose new insights beyond their well-defined meaning in development.
The following articles in journals at HighWire Press have cited this article:
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  J.-W. Lee, H. D. Han, M. M. K. Shahzad, S. W. Kim, L. S. Mangala, A. M. Nick, C. Lu, R. R. Langley, R. Schmandt, H.-S. Kim, et al. EphA2 Immunoconjugate as Molecularly Targeted Chemotherapy for Ovarian Carcinoma J Natl Cancer Inst, September 2, 2009; 101(17): 1193 - 1205. [Abstract] [Full Text] [PDF]
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 J. Wykosky and W. Debinski The EphA2 Receptor and EphrinA1 Ligand in Solid Tumors: Function and Therapeutic Targeting Mol. Cancer Res., December 1, 2008; 6(12): 1795 - 1806. [Abstract] [Full Text] [PDF]
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 D. Jackson, J. Gooya, S. Mao, K. Kinneer, L. Xu, M. Camara, C. Fazenbaker, R. Fleming, S. Swamynathan, D. Meyer, et al. A Human Antibody-Drug Conjugate Targeting EphA2 Inhibits Tumor Growth In vivo Cancer Res., November 15, 2008; 68(22): 9367 - 9374. [Abstract] [Full Text] [PDF]
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R. Buettner, T. Mesa, A. Vultur, F. Lee, and R. Jove Inhibition of Src Family Kinases with Dasatinib Blocks Migration and Invasion of Human Melanoma Cells Mol. Cancer Res., November 1, 2008; 6(11): 1766 - 1774. [Abstract] [Full Text] [PDF]
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 F. J. Torres-Velez, W. -J. Shieh, P. E. Rollin, T. Morken, C. Brown, T. G. Ksiazek, and S. R. Zaki Histopathologic and Immunohistochemical Characterization of Nipah Virus Infection in the Guinea Pig Vet. Pathol., July 1, 2008; 45(4): 576 - 585. [Abstract] [Full Text] [PDF]
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A. B. Larsen, M. W. Pedersen, M.-T. Stockhausen, M. V. Grandal, B. v. Deurs, and H. S. Poulsen Activation of the EGFR Gene Target EphA2 Inhibits Epidermal Growth Factor-Induced Cancer Cell Motility Mol. Cancer Res., March 1, 2007; 5(3): 283 - 293. [Abstract] [Full Text] [PDF]
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 A. K. Jassen, H. Yang, G. M. Miller, E. Calder, and B. K. Madras Receptor Regulation of Gene Expression of Axon Guidance Molecules: Implications for Adaptation Mol. Pharmacol., July 1, 2006; 70(1): 71 - 77. [Abstract] [Full Text] [PDF]
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 T. Korff, G. Dandekar, D. Pfaff, T. Fuller, W. Goettsch, H. Morawietz, F. Schaffner, and H. G. Augustin Endothelial EphrinB2 Is Controlled by Microenvironmental Determinants and Associates Context-Dependently With CD31 Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 468 - 474. [Abstract] [Full Text] [PDF]
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 M. I. Bonaparte, A. S. Dimitrov, K. N. Bossart, G. Crameri, B. A. Mungall, K. A. Bishop, V. Choudhry, D. S. Dimitrov, L.-F. Wang, B. T. Eaton, et al. From The Cover: Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus PNAS, July 26, 2005; 102(30): 10652 - 10657. [Abstract] [Full Text] [PDF]
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 A. Liu, C. Stadelmann, M. Moscarello, W. Bruck, A. Sobel, F. G. Mastronardi, and P. Casaccia-Bonnefil Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders J. Neurosci., January 19, 2005; 25(3): 737 - 747. [Abstract] [Full Text] [PDF]
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 Y. Tamimi, M. Lines, M. Coca-Prados, and M. A. Walter Identification of Target Genes Regulated by FOXC1 Using Nickel Agarose-Based Chromatin Enrichment Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3904 - 3913. [Abstract] [Full Text] [PDF]
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R. van Doorn, R. Dijkman, M. H. Vermeer, J. J. Out-Luiting, E. M. H. van der Raaij-Helmer, R. Willemze, and C. P. Tensen Aberrant Expression of the Tyrosine Kinase Receptor EphA4 and the Transcription Factor Twist in Sezary Syndrome Identified by Gene Expression Analysis Cancer Res., August 15, 2004; 64(16): 5578 - 5586. [Abstract] [Full Text] [PDF]
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