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Vol. 75, No. 5, 2008
Issue release date: October 2008
Pathobiology 2008;75:274–280
(DOI:10.1159/000151707)

EphB1 Is Underexpressed in Poorly Differentiated Colorectal Cancers

Sheng Z.a · Wang J.a, b · Dong Y.a · Ma H.a · Zhou H.a · Sugimura H.c · Lu G.b · Zhou X.a
aDepartment of Pathology, Clinical School of Medical College of Nanjing University/Nanjing Jinling Hospital, and bCenter for Molecular Imaging Research, Department of Radiology, Nanjing Jinling Hospital, Nanjing, PR China; cDepartment of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
email Corresponding Author

Abstract

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.


 goto top of outline Key Words

  • EphB1
  • Colorectal cancer
  • Quantitative real-time RT-PCR
  • Immunohistochemical staining

 goto top of outline Abstract

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.

Copyright © 2008 S. Karger AG, Basel


 goto top of outline References
  1. Hirai H, Maru Y, Hagiwara K, Nishida J, Takaku F: A novel putative tyrosine kinase receptor encoded by the eph gene. Science 1987;238:1717–1720.
  2. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell 1997;90:403–404.
  3. Kojima T, Chang JH, Azar DT: Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis. Am J Pathol 2007;170:764–773.
  4. Chumley MJ, Catchpole T, Silvany RE, Kernie SG, Henkemeyer M: EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. J Neurosci 2007;27:13481–13490.
  5. Kadison SR, Makinen T, Klein R, Henkemeyer M, Kaprielian Z: EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord. J Neurosci 2006;26:8909–8914.
  6. Jevince AR, Kadison SR, Pittman AJ, Chien CB, Kaprielian Z: Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal cord. J Comp Neurol 2006;497:734–750.
  7. Gerety SS, Anderson DJ: Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. Development 2002;129:1397–1410.
  8. Wang J, Kataoka H, Suzuki M, Sato N, Nakamura R, Tao H, Maruyama K, Isogaki J, Kanaoka S, Ihara M, Tanaka M, Kanamori M, Nakamura T, Shinmura K, Sugimura H: Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene 2005;24:5637–5647.
  9. Wang J, Li G, Ma H, Bao Y, Wang X, Zhou H, Sheng Z, Sugimura H, Jin J, Zhou X: Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. Hum Pathol 2007;38:1649–1656.
  10. Cortina C, Palomo-Ponce S, Iglesias M, Fernandez-Masip JL, Vivancos A, Whissell G, Huma M, Peiro N, Gallego L, Jonkheer S, Davy A, Lloreta J, Sancho E, Batlle E: EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet 2007;39:1376–1383.
  11. Holmberg J, Genander M, Halford MM, Anneren C, Sondell M, Chumley MJ, Silvany RE, Henkemeyer M, Frisen J: EphB receptors coordinate migration and proliferation in the intestinal stem cell niche. Cell 2006;125:1151–1163.
  12. Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, Meeldijk J, Robertson J, van de Wetering M, Pawson T, Clevers H: β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002;111:251–263.
  13. Clark SJ, Harrison J, Paul CL, Frommer M: High sensitivity mapping of methylated cytosines. Nucleic Acids Res 1994;22:2990–2997.
  14. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CPG islands. Proc Natl Acad Sci USA 1996;93:9821–9826.
  15. Batlle E, Bacani J, Begthel H, Jonkheer S, Gregorieff A, van de Born M, Malats N, Sancho E, Boon E, Pawson T, Gallinger S, Pals S, Clevers H: EphB receptor activity suppresses colorectal cancer progression. Nature 2005;435:1126–1130.
  16. Davalos V, Dopeso H, Castano J, Wilson AJ, Vilardell F, Romero-Gimenez J, Espin E, Armengol M, Capella G, Mariadason JM, Aaltonen LA, Schwartz S Jr, Arango D: EphB4 and survival of colorectal cancer patients. Cancer Res 2006;66:8943–8948.
  17. Jubb AM, Zhong F, Bheddah S, Grabsch HI, Frantz GD, Mueller W, Kavi V, Quirke P, Polakis P, Koeppen H: EphB2 is a prognostic factor in colorectal cancer. Clin Cancer Res 2005;11:5181–5187.

 goto top of outline Author Contacts

Xiaojun Zhou, MD, PhD
Department of Pathology
Nanjing University School of Medicine/Nanjing Jinling Hospital
Nanjing 210002 (PR China)
Tel. +86 25 8086 1292, Fax +86 25 8086 0191, E-Mail nanjing_81@yahoo.com


 goto top of outline Article Information

Z.S. and J.W. contributed equally to this paper.

Received: September 19, 2007
Accepted after revision: February 18, 2008
Published online: October 15, 2008
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 3, Number of References : 17


 goto top of outline Publication Details

Pathobiology (Exploring the basis of disease)

Vol. 75, No. 5, Year 2008 (Cover Date: October 2008)

Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)

For additional information: http://www.karger.com/PAT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Over- or underexpression of certain Eph receptors has been associated with tumorigenesis of some types of cancer. EphB1 is a member of receptor tyrosine kinases of the EphB subfamily involved in the development, progress and prognosis of colorectal cancers. The expression levels of EphB1 in colon cancer cell lines and human colorectal carcinoma specimens were determined and association of EphB1 expression with clinicopathological parameters was analyzed. Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry were used. Results: The EphB1 transcript is expressed in all colon cancer cell lines tested. However, there is marked variability in the expression of the EphB1 transcripts and proteins among colorectal carcinoma specimens. Reduced expression of EphB1 in colorectal cancers more often occurred in poorly differentiated and mucinous adenocarcinomas than in well- and moderately differentiated adenocarcinomas. Further, cancer cells with a low level of EphB1 protein showed more invasive power. Conclusion: Our data indicate that EphB1 may have roles in the pathogenesis and development of colorectal cancer.



 goto top of outline Author Contacts

Xiaojun Zhou, MD, PhD
Department of Pathology
Nanjing University School of Medicine/Nanjing Jinling Hospital
Nanjing 210002 (PR China)
Tel. +86 25 8086 1292, Fax +86 25 8086 0191, E-Mail nanjing_81@yahoo.com


 goto top of outline Article Information

Z.S. and J.W. contributed equally to this paper.

Received: September 19, 2007
Accepted after revision: February 18, 2008
Published online: October 15, 2008
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 3, Number of References : 17


 goto top of outline Publication Details

Pathobiology (Exploring the basis of disease)

Vol. 75, No. 5, Year 2008 (Cover Date: October 2008)

Journal Editor: Borisch B. (Geneva), Yasui W. (Hiroshima)
ISSN: 1015–2008 (Print), eISSN: 1423–0291 (Online)

For additional information: http://www.karger.com/PAT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Hirai H, Maru Y, Hagiwara K, Nishida J, Takaku F: A novel putative tyrosine kinase receptor encoded by the eph gene. Science 1987;238:1717–1720.
  2. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell 1997;90:403–404.
  3. Kojima T, Chang JH, Azar DT: Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis. Am J Pathol 2007;170:764–773.
  4. Chumley MJ, Catchpole T, Silvany RE, Kernie SG, Henkemeyer M: EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. J Neurosci 2007;27:13481–13490.
  5. Kadison SR, Makinen T, Klein R, Henkemeyer M, Kaprielian Z: EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord. J Neurosci 2006;26:8909–8914.
  6. Jevince AR, Kadison SR, Pittman AJ, Chien CB, Kaprielian Z: Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal cord. J Comp Neurol 2006;497:734–750.
  7. Gerety SS, Anderson DJ: Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. Development 2002;129:1397–1410.
  8. Wang J, Kataoka H, Suzuki M, Sato N, Nakamura R, Tao H, Maruyama K, Isogaki J, Kanaoka S, Ihara M, Tanaka M, Kanamori M, Nakamura T, Shinmura K, Sugimura H: Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene 2005;24:5637–5647.
  9. Wang J, Li G, Ma H, Bao Y, Wang X, Zhou H, Sheng Z, Sugimura H, Jin J, Zhou X: Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. Hum Pathol 2007;38:1649–1656.
  10. Cortina C, Palomo-Ponce S, Iglesias M, Fernandez-Masip JL, Vivancos A, Whissell G, Huma M, Peiro N, Gallego L, Jonkheer S, Davy A, Lloreta J, Sancho E, Batlle E: EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet 2007;39:1376–1383.
  11. Holmberg J, Genander M, Halford MM, Anneren C, Sondell M, Chumley MJ, Silvany RE, Henkemeyer M, Frisen J: EphB receptors coordinate migration and proliferation in the intestinal stem cell niche. Cell 2006;125:1151–1163.
  12. Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, Meeldijk J, Robertson J, van de Wetering M, Pawson T, Clevers H: β-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002;111:251–263.
  13. Clark SJ, Harrison J, Paul CL, Frommer M: High sensitivity mapping of methylated cytosines. Nucleic Acids Res 1994;22:2990–2997.
  14. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CPG islands. Proc Natl Acad Sci USA 1996;93:9821–9826.
  15. Batlle E, Bacani J, Begthel H, Jonkheer S, Gregorieff A, van de Born M, Malats N, Sancho E, Boon E, Pawson T, Gallinger S, Pals S, Clevers H: EphB receptor activity suppresses colorectal cancer progression. Nature 2005;435:1126–1130.
  16. Davalos V, Dopeso H, Castano J, Wilson AJ, Vilardell F, Romero-Gimenez J, Espin E, Armengol M, Capella G, Mariadason JM, Aaltonen LA, Schwartz S Jr, Arango D: EphB4 and survival of colorectal cancer patients. Cancer Res 2006;66:8943–8948.
  17. Jubb AM, Zhong F, Bheddah S, Grabsch HI, Frantz GD, Mueller W, Kavi V, Quirke P, Polakis P, Koeppen H: EphB2 is a prognostic factor in colorectal cancer. Clin Cancer Res 2005;11:5181–5187.