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Erschienen in: Annals of Surgical Oncology 5/2007

01.05.2007 | Head

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

verfasst von: Chul-Ho Kim, MD, PhD, JangHee Kim, MD, Hison Kahng, MD, Eun Chang Choi, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 5/2007

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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.
Literatur
1.
Zurück zum Zitat 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; 92:4412–6PubMedCrossRef 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; 92:4412–6PubMedCrossRef
2.
Zurück zum Zitat Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 1991; 67:901–8PubMedCrossRef Montesano R, Matsumoto K, Nakamura T, Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 1991; 67:901–8PubMedCrossRef
3.
Zurück zum Zitat Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 342:440–3PubMedCrossRef Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 342:440–3PubMedCrossRef
4.
Zurück zum Zitat Zarnegar R, Michalopoulos GK. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. J Cell Biol 1995; 129:1177–80PubMedCrossRef Zarnegar R, Michalopoulos GK. The many faces of hepatocyte growth factor: from hepatopoiesis to hematopoiesis. J Cell Biol 1995; 129:1177–80PubMedCrossRef
5.
Zurück zum Zitat 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; 84:1150–8PubMed 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; 84:1150–8PubMed
6.
Zurück zum Zitat Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251:802–4PubMedCrossRef Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251:802–4PubMedCrossRef
7.
Zurück zum Zitat 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; 55:1129–38PubMed 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; 55:1129–38PubMed
8.
Zurück zum Zitat Kim CH, Moon SK, Bae JH, et al. Expression of hepatocyte growth factor and c-Met in hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 2006; 126:88–94PubMedCrossRef Kim CH, Moon SK, Bae JH, et al. Expression of hepatocyte growth factor and c-Met in hypopharyngeal squamous cell carcinoma. Acta Otolaryngol 2006; 126:88–94PubMedCrossRef
9.
Zurück zum Zitat Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251:1451–5PubMedCrossRef Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251:1451–5PubMedCrossRef
10.
Zurück zum Zitat 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):513–21PubMed 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):513–21PubMed
11.
Zurück zum Zitat 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; 425:139–44PubMedCrossRef 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; 425:139–44PubMedCrossRef
12.
Zurück zum Zitat 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; 58:1064–9PubMedCrossRef 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; 58:1064–9PubMedCrossRef
13.
Zurück zum Zitat 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; 125:1327–40PubMedCrossRef 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; 125:1327–40PubMedCrossRef
14.
Zurück zum Zitat 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; 4:834–9PubMedCrossRef 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; 4:834–9PubMedCrossRef
15.
Zurück zum Zitat 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; 20:1385–90PubMed 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; 20:1385–90PubMed
16.
Zurück zum Zitat 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; 55:580–5PubMedCrossRef 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; 55:580–5PubMedCrossRef
17.
Zurück zum Zitat 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; 127:59–63PubMedCrossRef 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; 127:59–63PubMedCrossRef
18.
Zurück zum Zitat 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; 18:219–28PubMedCrossRef 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; 18:219–28PubMedCrossRef
19.
Zurück zum Zitat 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; 19:381–4PubMed 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; 19:381–4PubMed
20.
Zurück zum Zitat Boros P, Miller CM. Hepatocyte growth factor: a multifunctional cytokine. Lancet 1995; 345:293–5PubMedCrossRef Boros P, Miller CM. Hepatocyte growth factor: a multifunctional cytokine. Lancet 1995; 345:293–5PubMedCrossRef
21.
Zurück zum Zitat Grant DS, Kleinman HK, Goldberg ID, et al. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A 1993; 90:1937–41PubMedCrossRef Grant DS, Kleinman HK, Goldberg ID, et al. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A 1993; 90:1937–41PubMedCrossRef
22.
Zurück zum Zitat Wang Y, Selden AC, Morgan N, Stamp GW, Hodgson HJ. Hepatocyte growth factor/scatter factor expression in human mammary epithelium. Am J Pathol 1994; 144:675–82PubMed Wang Y, Selden AC, Morgan N, Stamp GW, Hodgson HJ. Hepatocyte growth factor/scatter factor expression in human mammary epithelium. Am J Pathol 1994; 144:675–82PubMed
23.
Zurück zum Zitat 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; 1:295–305PubMed 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; 1:295–305PubMed
24.
Zurück zum Zitat Hiscox S, Jiang WG. Hepatocyte growth factor/scatter factor disrupts epithelial tumour cell-cell adhesion: involvement of beta-catenin. Anticancer Res 1999; 19:509–17PubMed Hiscox S, Jiang WG. Hepatocyte growth factor/scatter factor disrupts epithelial tumour cell-cell adhesion: involvement of beta-catenin. Anticancer Res 1999; 19:509–17PubMed
25.
Zurück zum Zitat 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; 20:8125–35PubMedCrossRef 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; 20:8125–35PubMedCrossRef
26.
Zurück zum Zitat 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; 276:24661–6PubMedCrossRef 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; 276:24661–6PubMedCrossRef
27.
Zurück zum Zitat 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; 25:3534–45PubMedCrossRef 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; 25:3534–45PubMedCrossRef
Metadaten
Titel
Change of E-Cadherin by Hepatocyte Growth Factor and Effects on the Prognosis of Hypopharyngeal Carcinoma
verfasst von
Chul-Ho Kim, MD, PhD
JangHee Kim, MD
Hison Kahng, MD
Eun Chang Choi, MD, PhD
Publikationsdatum
01.05.2007
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 5/2007
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9320-5

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