Breast Cancer Research and Treatment

, Volume 106, Issue 3, pp 361–369

On the role of endothelin-converting enzyme-1 (ECE-1) and neprilysin in human breast cancer

  • Martin Smollich
  • Martin Götte
  • George W. Yip
  • Eng-Siang Yong
  • Christian Kersting
  • Jeanett Fischgräbe
  • Isabel Radke
  • Ludwig Kiesel
  • Pia Wülfing
Preclinical Study

Abstract

Endothelin-1 (ET-1) and its receptors, ETAR and ETBR, are overexpressed in breast carcinomas. However, little is known about the relevance of endothelin-converting enzyme-1 (ECE-1) and ET-1 degrading neprilysin (NEP). In this study, expression of ECE-1 and NEP was determined in 600 breast cancer tissue samples by immunohistochemistry; staining results were correlated with clinicopathological parameters. For ECE-1 expression, we found a significant correlation with VEGF (P < 0.001) and ETAR expression (P = 0.048). While patients with ECE-1 overexpressing tumours had more frequent disease recurrence (P = 0.03), NEP overexpression correlated with improved disease-free survival (DFS) (P = 0.023) and less frequent metastasis (P = 0.046). Also, a decrease of NEP expression with malignant progression (G1–G3) was found. ECE-1 inhibition using the selective ECE-1 inhibitor RO 67-7447 in MCF-7 breast cancer cells led to a significantly decreased ET-1 expression and reduced cell invasiveness (54.3% of controls, P = 0.014). Our results indicate that overexpression of ECE-1 is associated with unfavourable outcome, whereas NEP positively influences survival. Thus, expression of ECE-1 and NEP may have prognostic relevance. Due to the anti-invasive effect of the selective ECE-1 inhibitor, targeting ECE-1 may represent an innovative option in future breast cancer therapy.

Keywords

Breast cancer Endothelin Endothelin-converting enzyme Neprilysin RO 67-7447 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Martin Smollich
    • 1
  • Martin Götte
    • 1
  • George W. Yip
    • 2
  • Eng-Siang Yong
    • 2
  • Christian Kersting
    • 3
  • Jeanett Fischgräbe
    • 1
  • Isabel Radke
    • 1
  • Ludwig Kiesel
    • 1
  • Pia Wülfing
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity Hospital of MünsterMünsterGermany
  2. 2.Department of Anatomy, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  3. 3.Gerhard-Domagk-Institute of PathologyUniversity of MünsterMunsterGermany

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