Skip to main content

Advertisement

SpringerLink
Log in

Change of E-Cadherin by Hepatocyte Growth Factor and Effects on the Prognosis of Hypopharyngeal Carcinoma

  • Head
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma.

Methods

Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma were evaluated for the expression of HGF, its receptor (c-Met), and E-cadherin. Reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot test were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay.

Results

E-cadherin expression was found in 87.9% of squamous cell carcinomas; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1%). The expression of HGF in tumors with nonmembranous type E-cadherin expression was far higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (P < .05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (P < .05).

Conclusions

These results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.
FIG. 6.
FIG. 7.

Similar content being viewed by others

REFERENCES

  1. Barros EJ, Santos OF, Matsumoto K, Nakamura T, Nigam SK. Differential tubulogenic and branching morphogenetic activities of growth factors: implications for epithelial tissue development. Proc Natl Acad Sci U S A 1995; 92:4412–6

    Article  PubMed  CAS  Google Scholar 

  2. Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 1991; 67:901–8

    Article  PubMed  CAS  Google Scholar 

  3. Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 342:440–3

    Article  PubMed  CAS  Google Scholar 

  4. Zarnegar R, Michalopoulos GK. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. J Cell Biol 1995; 129:1177–80

    Article  PubMed  CAS  Google Scholar 

  5. Yoshinaga Y, Matsuno Y, Fujita S, et al. Immunohistochemical detection of hepatocyte growth factor/scatter factor in human cancerous and inflammatory lesions of various organs. Jpn J Cancer Res 1993; 84:1150–8

    PubMed  CAS  Google Scholar 

  6. Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251:802–4

    Article  PubMed  CAS  Google Scholar 

  7. Di Renzo MF, Poulsom R, Olivero M, Comoglio PM, Lemoine NR. Expression of the Met/hepatocyte growth factor receptor in human pancreatic cancer. Cancer Res 1995; 55:1129–38

    PubMed  CAS  Google Scholar 

  8. Kim CH, Moon SK, Bae JH, et al. Expression of hepatocyte growth factor and c-Met in hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 2006; 126:88–94

    Article  PubMed  CAS  Google Scholar 

  9. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251:1451–5

    Article  PubMed  CAS  Google Scholar 

  10. Fabre M, Garcia de Herreros A. Phorbol ester–induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin. J Cell Sci 1993; 106(pt 2):513–21

    PubMed  CAS  Google Scholar 

  11. Tannapfel A, Yasui W, Yokozaki H, Wittekind C, Tahara E. Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines. Virchows Arch 1994; 425:139–44

    Article  PubMed  CAS  Google Scholar 

  12. Miura H, Nishimura K, Tsujimura A, et al. Effects of hepatocyte growth factor on E-cadherin–mediated cell-cell adhesion in DU145 prostate cancer cells. Urology 2001; 58:1064–9

    Article  PubMed  CAS  Google Scholar 

  13. Hinck L, Nathke IS, Papkoff J, Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol 1994; 125:1327–40

    Article  PubMed  CAS  Google Scholar 

  14. Tsukita S, Tsukita S, Nagafuchi A, Yonemura S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr Opin Cell Biol 1992; 4:834–9

    Article  PubMed  CAS  Google Scholar 

  15. Wu H, Lotan R, Menter D, Lippman SM, Xu XC. Expression of E-cadherin is associated with squamous differentiation in squamous cell carcinomas. Anticancer Res 2000; 20:1385–90

    PubMed  CAS  Google Scholar 

  16. Mattijssen V, Peters HM, Schalkwijk L, et al. E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer 1993; 55:580–5

    Article  PubMed  CAS  Google Scholar 

  17. Chow V, Yuen AP, Lam KY, Tsao GS, Ho WK, Wei WI. A comparative study of the clinicopathological significance of E-cadherin and catenins (alpha, beta, gamma) expression in the surgical management of oral tongue carcinoma. J Cancer Res Clin Oncol 2001; 127:59–63

    Article  PubMed  CAS  Google Scholar 

  18. Nakayama S, Sasaki A, Mese H, Alcalde RE, Matsumura T. Establishment of high and low metastasis cell lines derived from a human tongue squamous cell carcinoma. Invasion Metastasis 1998; 18:219–28

    Article  PubMed  Google Scholar 

  19. Schipper JH, Unger A, Jahnke K. E-cadherin as a functional marker of the differentiation and invasiveness of squamous cell carcinoma of the head and neck. Clin Otolaryngol Allied Sci 1994; 19:381–4

    PubMed  CAS  Google Scholar 

  20. Boros P, Miller CM. Hepatocyte growth factor: a multifunctional cytokine. Lancet 1995; 345:293–5

    Article  PubMed  CAS  Google Scholar 

  21. Grant DS, Kleinman HK, Goldberg ID, et al. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A 1993; 90:1937–41

    Article  PubMed  CAS  Google Scholar 

  22. Wang Y, Selden AC, Morgan N, Stamp GW, Hodgson HJ. Hepatocyte growth factor/scatter factor expression in human mammary epithelium. Am J Pathol 1994; 144:675–82

    PubMed  CAS  Google Scholar 

  23. Shibamoto S, Hayakawa M, Takeuchi K, et al. Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes Commun 1994; 1:295–305

    PubMed  CAS  Google Scholar 

  24. Hiscox S, Jiang WG. Hepatocyte growth factor/scatter factor disrupts epithelial tumour cell-cell adhesion: involvement of beta-catenin. Anticancer Res 1999; 19:509–17

    PubMed  CAS  Google Scholar 

  25. Li G, Schaider H, Satyamoorthy K, Hanakawa Y, Hashimoto K, Herlyn M. Downregulation of E-cadherin and desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene 2001; 20:8125–35

    Article  PubMed  CAS  Google Scholar 

  26. Poser I, Dominguez D, de Herreros AG, Varnai A, Buettner R, Bosserhoff AK. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem 2001; 276:24661–6

    Article  PubMed  CAS  Google Scholar 

  27. Grotegut S, von Schweinitz D, Christofori G, Lehembre F. Hepatocyte growth factor induces cell scattering through MAPK/Egr-1–mediated upregulation of Snail. EMBO J 2006; 25:3534–45

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENT

Supported in part by CCRB through the “GRRC” Project of Gyeonggi Provincial Government, Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea

    Chul-Ho Kim MD, PhD & Hison Kahng MD

  2. Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Korea

    Chul-Ho Kim MD, PhD & Hison Kahng MD

  3. Department of Pathology, School of Medicine, Ajou University, Suwon, Korea

    JangHee Kim MD

  4. Department of Otorhinolaryngology, College of Medicine, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul, 120-752, Korea

    Eun Chang Choi MD, PhD

Authors
  1. Chul-Ho Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. JangHee Kim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hison Kahng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eun Chang Choi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eun Chang Choi MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, CH., Kim, J., Kahng, H. et al. Change of E-Cadherin by Hepatocyte Growth Factor and Effects on the Prognosis of Hypopharyngeal Carcinoma. Ann Surg Oncol 14, 1565–1574 (2007). https://doi.org/10.1245/s10434-006-9320-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-006-9320-5

Keywords

Search

Navigation