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

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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

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Nakajima, S., Doi, R., Toyoda, E., Tsuji, S., Wada, M., Koizumi, M., Tulachan, S. S., 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, 10(12 I), 4125-4133. https://doi.org/10.1158/1078-0432.CCR-0578-03