Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

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.

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

Similar content being viewed by others

References

  1. Malassiné A, Cronier L. Involvement of gap junctions in placental functions and development. Biochim Biophys Acta. 2005;1719(1–2):117–24.

    PubMed  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  PubMed  CAS  Google Scholar 

  4. El-Sabban ME, Pauli BU. Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium. J Cell Biol. 1991;115(5):1375–82.

    Article  PubMed  CAS  Google Scholar 

  5. 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. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Prochnow N, Dermietzel R. Connexons and cell adhesion: a romantic phase. Histochem Cell Biol. 2008;130(1):71–7.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008;14(24):3792–7.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Rubin H. Contact interactions between cells that suppress neoplastic development: can they also explain metastatic dormancy? Adv Cancer Res. 2008;100(2):159–202.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. Elias LA, Wang DD, Kriegstein AR. Gap junction adhesion is necessary for radial migration in the neocortex. Nature. 2007;448(7156):901–7.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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  Google Scholar 

Download references

Acknowledgments

This work was supported by grant No. 30801097 from the National Natural Science Foundation of China.

Author information

Authors and Affiliations

  1. General Surgery Center of PLA, Southwest Hospital, The Third Military Medical University, Gaotanyan Street, 400038, Shapingba District, Chongqing, China

    Bo Tang, Pei-Wu Yu, Ge Yu & Feng Qian

  2. Institute of Digestive Diseases, Southwest Hospital, The Third Military Medical University, Gaotanyan Street, 400038, Shapingba District, Chongqing, China

    Zhi-Hong Peng

Authors
  1. Bo Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-Hong Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pei-Wu Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ge Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pei-Wu Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, B., Peng, ZH., Yu, PW. et al. Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes. Med Oncol 28, 502–508 (2011). https://doi.org/10.1007/s12032-010-9492-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9492-5

Keywords

Search

Navigation