Publication

Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades

Evans, J. J., Chitcholtan, K., Dann, J. M., Guilford, P., Harris, G., Lewis, L. K., Nagase, J., Welkamp, A. A. W., Zwerus, R. & Sykes, P. H., Apr-2012, In : Gynecologic Oncology. 125, 1, p. 214-219 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • J. J. Evans
  • K. Chitcholtan
  • J. M. Dann
  • P. Guilford
  • Gavin Harris
  • L. K. Lewis
  • J. Nagase
  • A. A. W. Welkamp
  • R. Zwerus
  • P. H. Sykes

Objective. Endometrial cancer, in developed countries, is the most common malignancy of the female genital tract. Surgery and radiotherapy are successful in many patients but systemic and recurrent diseases have no consistently effective treatments, and for high grade advanced disease the prognosis is poor. The study investigated characteristics of adrenomedullin in endometrial cancer to assist in identifying targets for developing treatments.

Methods. Endometrial samples of women with and without cancer, and the Ishikawa cell line were used to investigate adrenomedullin mRNA regulation, peptide expression, adrenomedullin secretion and effects of adrenomedullin on VEGF secretion.

Results. Expression of adrenomedullin mRNA was upregulated compared to that in healthy post-menopausal endometria. Adrenomedullin secretion was increased by cobalt chloride in this study. Secretion was reduced by the naturally-occurring compounds, (-)-epigallocatechin gallate (EGCG) and 3,4',5-trihydroxystilbene (resveratrol), which we have previously demonstrated to also suppress VEGF secretion in endometrial tumour tissue. We noted, for the first time, that adrenomedullin enhanced VEGF secretion from tumour cells.

Conclusions. Increased adrenomedullin expression may result in amplifying both tumorigenic and angiogenic activities. A substantial impact on growth of tumours may result in vivo as a consequence of the synergism between adrenomedullin and VEGF. Adrenomedullin, which has altered cellular characteristics in tumour compared to healthy tissue, offers an understudied target with potential to modify endometrial cancer behaviour, complementing other treatments. (C) 2011 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)214-219
Number of pages6
JournalGynecologic Oncology
Volume125
Issue number1
Publication statusPublished - Apr-2012

    Keywords

  • Adrenomedullin, Endometrial cancer, EGCG, Resveratrol, Vascular endothelial growth factor, Natural compound, POSSIBLE PROMOTION MECHANISM, ENDOTHELIAL GROWTH-FACTOR, ESTROGEN-RECEPTOR, GENE-EXPRESSION, CARCINOMA CELLS, HYPOXIA, ANGIOGENESIS, AUTOCRINE, INDUCTION, PLASMA

ID: 5527563