N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma

Sanae Nakajima, Ryuichiro Doi, Eiji Toyoda, Shoichiro Tsuji, Michihiko Wada, Masayuki Koizumi, Sidhartha S. Tulachan, Daisuke Ito, Kazuhiro Kami, Tomohiko Mori, Yoshiya Kawaguchi, Koji Fujimoto, Ryo Hosotani, Masayuki Imamura

Research output: Contribution to journalArticle

263 Citations (Scopus)

Abstract

Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to- mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF4 stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.

Original languageEnglish
Pages (from-to)4125-4133
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number12 I
DOIs
Publication statusPublished - 15-07-2004

Fingerprint

Epithelial-Mesenchymal Transition
Cadherins
Vimentin
Neoplasms
Intercellular Signaling Peptides and Proteins
Transforming Growth Factors
Neoplasm Metastasis
Pancreatic Carcinoma
Fibroblast Growth Factors
Cell Adhesion Molecules
Fibroblast Growth Factor 2
Pancreatic Neoplasms
Cell Movement
Cultured Cells
Research Design
Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Nakajima, Sanae ; Doi, Ryuichiro ; Toyoda, Eiji ; Tsuji, Shoichiro ; Wada, Michihiko ; Koizumi, Masayuki ; Tulachan, Sidhartha S. ; Ito, Daisuke ; Kami, Kazuhiro ; Mori, Tomohiko ; Kawaguchi, Yoshiya ; Fujimoto, Koji ; Hosotani, Ryo ; Imamura, Masayuki. / N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 12 I. pp. 4125-4133.
@article{74924b9065164bc0b54480bd068d25aa,
title = "N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma",
abstract = "Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to- mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF4 stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.",
author = "Sanae Nakajima and Ryuichiro Doi and Eiji Toyoda and Shoichiro Tsuji and Michihiko Wada and Masayuki Koizumi and Tulachan, {Sidhartha S.} and Daisuke Ito and Kazuhiro Kami and Tomohiko Mori and Yoshiya Kawaguchi and Koji Fujimoto and Ryo Hosotani and Masayuki Imamura",
year = "2004",
month = "7",
day = "15",
doi = "10.1158/1078-0432.CCR-0578-03",
language = "English",
volume = "10",
pages = "4125--4133",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12 I",

}

Nakajima, S, Doi, R, Toyoda, E, Tsuji, S, Wada, M, Koizumi, M, Tulachan, SS, Ito, D, Kami, K, Mori, T, Kawaguchi, Y, Fujimoto, K, Hosotani, R & Imamura, M 2004, 'N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma', Clinical Cancer Research, vol. 10, no. 12 I, pp. 4125-4133. https://doi.org/10.1158/1078-0432.CCR-0578-03

N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. / Nakajima, Sanae; Doi, Ryuichiro; Toyoda, Eiji; Tsuji, Shoichiro; Wada, Michihiko; Koizumi, Masayuki; Tulachan, Sidhartha S.; Ito, Daisuke; Kami, Kazuhiro; Mori, Tomohiko; Kawaguchi, Yoshiya; Fujimoto, Koji; Hosotani, Ryo; Imamura, Masayuki.

In: Clinical Cancer Research, Vol. 10, No. 12 I, 15.07.2004, p. 4125-4133.

Research output: Contribution to journalArticle

TY - JOUR

T1 - N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma

AU - Nakajima, Sanae

AU - Doi, Ryuichiro

AU - Toyoda, Eiji

AU - Tsuji, Shoichiro

AU - Wada, Michihiko

AU - Koizumi, Masayuki

AU - Tulachan, Sidhartha S.

AU - Ito, Daisuke

AU - Kami, Kazuhiro

AU - Mori, Tomohiko

AU - Kawaguchi, Yoshiya

AU - Fujimoto, Koji

AU - Hosotani, Ryo

AU - Imamura, Masayuki

PY - 2004/7/15

Y1 - 2004/7/15

N2 - Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to- mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF4 stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.

AB - Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to- mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. Experimental Design: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)β and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. Results: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF4 stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. Conclusion: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.

UR - http://www.scopus.com/inward/record.url?scp=3042618951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042618951&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-0578-03

DO - 10.1158/1078-0432.CCR-0578-03

M3 - Article

VL - 10

SP - 4125

EP - 4133

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12 I

ER -