Skip to main content
Erschienen in: Medical Oncology 2/2011

01.06.2011 | Original Paper

Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes

verfasst von: Bo Tang, Zhi-Hong Peng, Pei-Wu Yu, Ge Yu, Feng Qian

Erschienen in: Medical Oncology | Ausgabe 2/2011

Einloggen, um Zugang zu erhalten

Abstract

Connexin 43(Cx43) and E-cadherin are concurrently expressed in many tumors and were ever classified as tumor suppressors in primary tumors (PT), whereas recent studies showed that these two proteins played specific roles in tumor metastasis. The aim of our study is to determine the expression of Cx43 and E-cadherin in primary gastric tumors (PTs) and matched metastatic lymph nodes (MLNs) and to explore the clinical and pathological implications of expression of these proteins. Immunohistochemical assay was conducted to detect the expression of Cx43 and E-cadherin in PTs and MLNs, and the clinical and pathological implications were analyzed by statistical methods. In PTs, the expression of Cx43 and E-cadherin was significantly reduced, compared to adjacent normal tissues (P < 0.01). The expression of Cx43 and E-cadherin was significantly increased in MLNs compared with PTs (P < 0.01 and P < 0.01, for Cx43 and E-cadherin, respectively), and some Cx43 and E-cadherin-negative PTs developed Cx43 and E-cadherin-positive MLNs. Furthermore, reduced expression of both Cx43 and E-cadherin significantly correlated with poor differentiation, advanced TNM stage, and lymph note metastasis of gastric cancers. Cx43 and E-cadherin expression significantly correlated with each other. We concluded that concurrent reduction in Cx43 and E-cadherin may contribute to the occurrence of gastric cancer. However, concurrent increased expression of Cx43 and E-cadherin may contribute to the efficient metastasis of gastric cancer to the lymph nodes.
Literatur
1.
Zurück zum Zitat Malassiné A, Cronier L. Involvement of gap junctions in placental functions and development. Biochim Biophys Acta. 2005;1719(1–2):117–24.PubMed Malassiné A, Cronier L. Involvement of gap junctions in placental functions and development. Biochim Biophys Acta. 2005;1719(1–2):117–24.PubMed
2.
Zurück zum Zitat Willecke K, Eiberger J, Degen J, et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem. 2002;383(5):725–37.PubMedCrossRef Willecke K, Eiberger J, Degen J, et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biol Chem. 2002;383(5):725–37.PubMedCrossRef
3.
Zurück zum Zitat Pahujaa M, Anikin M, Goldberg GS, et al. Phosphorylation of connexin43 induced by Src: regulation of gap junctional communication between transformed cells. Exp Cell Res. 2007;313(20):4083–90.PubMedCrossRef Pahujaa M, Anikin M, Goldberg GS, et al. Phosphorylation of connexin43 induced by Src: regulation of gap junctional communication between transformed cells. Exp Cell Res. 2007;313(20):4083–90.PubMedCrossRef
4.
Zurück zum Zitat El-Sabban ME, Pauli BU. Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium. J Cell Biol. 1991;115(5):1375–82.PubMedCrossRef El-Sabban ME, Pauli BU. Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium. J Cell Biol. 1991;115(5):1375–82.PubMedCrossRef
5.
Zurück zum Zitat El-Sabban ME, Pauli BU. Adhesion-mediated gap junctional communication between lung-metastatic cancer cells and endothelium. Invasion Metastasis. 1994–1995; 14(1–6):164–76. El-Sabban ME, Pauli BU. Adhesion-mediated gap junctional communication between lung-metastatic cancer cells and endothelium. Invasion Metastasis. 1994–1995; 14(1–6):164–76.
6.
Zurück zum Zitat Ito A, Katoh F, Kataoka TR, et al. A role for heterologous gap junctions between melanoma and endothelial cells in metastasis. J Clin Invest. 2000;105(9):1189–97.PubMedCrossRef Ito A, Katoh F, Kataoka TR, et al. A role for heterologous gap junctions between melanoma and endothelial cells in metastasis. J Clin Invest. 2000;105(9):1189–97.PubMedCrossRef
7.
Zurück zum Zitat Prochnow N, Dermietzel R. Connexons and cell adhesion: a romantic phase. Histochem Cell Biol. 2008;130(1):71–7.PubMedCrossRef Prochnow N, Dermietzel R. Connexons and cell adhesion: a romantic phase. Histochem Cell Biol. 2008;130(1):71–7.PubMedCrossRef
8.
Zurück zum Zitat Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28(1–2):151–66.PubMedCrossRef Schmalhofer O, Brabletz S, Brabletz T. E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 2009;28(1–2):151–66.PubMedCrossRef
9.
Zurück zum Zitat Tsanou E, Peschos D, Batistatou A, Charalabopoulos A, Charalabopoulos K. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res. 2008;28(6A):3815–26.PubMed Tsanou E, Peschos D, Batistatou A, Charalabopoulos A, Charalabopoulos K. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res. 2008;28(6A):3815–26.PubMed
10.
Zurück zum Zitat Nair KS, Naidoo R, Chetty R. Expression of cell adhesion molecules in esophageal carcinoma and its prognostic value. J Clin Pathol. 2005;58(4):343–51.PubMedCrossRef Nair KS, Naidoo R, Chetty R. Expression of cell adhesion molecules in esophageal carcinoma and its prognostic value. J Clin Pathol. 2005;58(4):343–51.PubMedCrossRef
11.
Zurück zum Zitat Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008;14(24):3792–7.PubMedCrossRef Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008;14(24):3792–7.PubMedCrossRef
12.
Zurück zum Zitat Xu HT, Li QC, Zhang YX, Zhao Y, Liu Y, Yang ZQ, et al. Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells. Folia Histochem Cytobiol. 2008;46(3):315–21.PubMedCrossRef Xu HT, Li QC, Zhang YX, Zhao Y, Liu Y, Yang ZQ, et al. Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells. Folia Histochem Cytobiol. 2008;46(3):315–21.PubMedCrossRef
13.
Zurück zum Zitat Li Z, Zhou Z, Donahue HJ. Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential. Clin Exp Metastasis. 2008;25(3):265–72.PubMedCrossRef Li Z, Zhou Z, Donahue HJ. Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential. Clin Exp Metastasis. 2008;25(3):265–72.PubMedCrossRef
14.
Zurück zum Zitat Krutovskikh V, Mazzoleni G, Mironov N, Omori Y, Aguelon AM, Mesnil M, et al. Expression of connexins 26, 32 and 43 in the human colon–an immunohistochemical study. Folia Histochem Cytobiol. 2004;42(4):203–7. Krutovskikh V, Mazzoleni G, Mironov N, Omori Y, Aguelon AM, Mesnil M, et al. Expression of connexins 26, 32 and 43 in the human colon–an immunohistochemical study. Folia Histochem Cytobiol. 2004;42(4):203–7.
15.
Zurück zum Zitat Krutovskikh V, Mazzoleni G, Mironov N, Omori Y, Aguelon AM, Mesnil M, et al. Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32. Int J Cancer. 1994;56(1):87–94.PubMedCrossRef Krutovskikh V, Mazzoleni G, Mironov N, Omori Y, Aguelon AM, Mesnil M, et al. Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32. Int J Cancer. 1994;56(1):87–94.PubMedCrossRef
16.
Zurück zum Zitat Krutovskikh VA, Troyanovsky SM, Piccoli C, Tsuda H, Asamoto M, Yamasaki H. Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo. Oncogene. 2000;19(4):505–13.PubMedCrossRef Krutovskikh VA, Troyanovsky SM, Piccoli C, Tsuda H, Asamoto M, Yamasaki H. Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo. Oncogene. 2000;19(4):505–13.PubMedCrossRef
17.
Zurück zum Zitat Rubin H. Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy? Adv Cancer Res. 2008;100(2):159–202.PubMedCrossRef Rubin H. Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy? Adv Cancer Res. 2008;100(2):159–202.PubMedCrossRef
18.
Zurück zum Zitat Kanczuga-Koda L, Sulkowski S, Lenczewski A, et al. Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer. J Clin Pathol. 2006;59(4):429–33.PubMedCrossRef Kanczuga-Koda L, Sulkowski S, Lenczewski A, et al. Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer. J Clin Pathol. 2006;59(4):429–33.PubMedCrossRef
19.
Zurück zum Zitat Pollmann MA, Shao Q, Laird DW, et al. Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture. Breast Cancer Res. 2005;7:R522–34.PubMedCrossRef Pollmann MA, Shao Q, Laird DW, et al. Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture. Breast Cancer Res. 2005;7:R522–34.PubMedCrossRef
20.
Zurück zum Zitat Ito A, Morita N, Miura D, Koma Y, Kataoka TR, Yamasaki H, et al. A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells. Carcinogenesis. 2004;25(10):2015–22.PubMedCrossRef Ito A, Morita N, Miura D, Koma Y, Kataoka TR, Yamasaki H, et al. A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells. Carcinogenesis. 2004;25(10):2015–22.PubMedCrossRef
21.
Zurück zum Zitat Kamibayashi Y, Oyamada Y, Mori M, Oyamada M. Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. Carcinogenesis. 1995;16(6):1287–97.PubMedCrossRef Kamibayashi Y, Oyamada Y, Mori M, Oyamada M. Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. Carcinogenesis. 1995;16(6):1287–97.PubMedCrossRef
22.
Zurück zum Zitat Elias LA, Wang DD, Kriegstein AR. Gap junction adhesion is necessary for radial migration in the neocortex. Nature. 2007;448(7156):901–7.PubMedCrossRef Elias LA, Wang DD, Kriegstein AR. Gap junction adhesion is necessary for radial migration in the neocortex. Nature. 2007;448(7156):901–7.PubMedCrossRef
23.
Zurück zum Zitat Xu X, Francis R, Wei CJ, et al. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells. Development. 2006;133(18):3629–39.PubMedCrossRef Xu X, Francis R, Wei CJ, et al. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells. Development. 2006;133(18):3629–39.PubMedCrossRef
24.
Zurück zum Zitat Pelin K, Hirvonen A, Linnainmaa K. Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells. Carcinogenesis. 1994;15(11):2673–5.PubMedCrossRef Pelin K, Hirvonen A, Linnainmaa K. Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells. Carcinogenesis. 1994;15(11):2673–5.PubMedCrossRef
25.
Zurück zum Zitat Kawasaki Y, Kubomoto A, Yamasaki H. Control of intracellular localization and function of Cx43 by SEMA3F. J Membr Biol. 2007;217(1–3):53–61.PubMedCrossRef Kawasaki Y, Kubomoto A, Yamasaki H. Control of intracellular localization and function of Cx43 by SEMA3F. J Membr Biol. 2007;217(1–3):53–61.PubMedCrossRef
26.
Zurück zum Zitat Karabekian Z, Gillum ND, Wong EW, Sarvazyan N. Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells. Cell Adh Migr. 2009;3(3):305–10.PubMedCrossRef Karabekian Z, Gillum ND, Wong EW, Sarvazyan N. Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells. Cell Adh Migr. 2009;3(3):305–10.PubMedCrossRef
27.
Zurück zum Zitat Huang T, Wan Y, Zhu Y, Fang X, Hiramatsu N, Hayakawa K, et al. Downregulation of gap junction expression and function by endoplasmic reticulum stress. J Cell Biochem. 2009;107(5):973–83.PubMedCrossRef Huang T, Wan Y, Zhu Y, Fang X, Hiramatsu N, Hayakawa K, et al. Downregulation of gap junction expression and function by endoplasmic reticulum stress. J Cell Biochem. 2009;107(5):973–83.PubMedCrossRef
28.
Zurück zum Zitat Yoon CS, Hyung WJ, Lee JH, Chae YS, Won NH, Yeom BW, et al. Expression of S100A4, E-cadherin, alpha-and beta-catenin in gastric adenocarcinoma. Hepatogastroenterology. 2008;55(86–87):1916–20.PubMed Yoon CS, Hyung WJ, Lee JH, Chae YS, Won NH, Yeom BW, et al. Expression of S100A4, E-cadherin, alpha-and beta-catenin in gastric adenocarcinoma. Hepatogastroenterology. 2008;55(86–87):1916–20.PubMed
Metadaten
Titel
Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes
verfasst von
Bo Tang
Zhi-Hong Peng
Pei-Wu Yu
Ge Yu
Feng Qian
Publikationsdatum
01.06.2011
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9492-5

Weitere Artikel der Ausgabe 2/2011

Medical Oncology 2/2011 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.