title: Adrenomedullin interacts with VEGF in endometrial cancer and has varied modulation in tumours of different grades.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Otago, Christchurch, Christchurch, New Zealand. john.evans@otago.ac.nz
authors.forename: J J
authors.initials: JJ
authors.lastname: Evans
authors.forename: K
authors.initials: K
authors.lastname: Chitcholtan
authors.forename: J M
authors.initials: JM
authors.lastname: Dann
authors.forename: P
authors.initials: P
authors.lastname: Guilford
authors.forename: Gavin
authors.initials: G
authors.lastname: Harris
authors.forename: L K
authors.initials: LK
authors.lastname: Lewis
authors.forename: J
authors.initials: J
authors.lastname: Nagase
authors.forename: A A W
authors.initials: AA
authors.lastname: Welkamp
authors.forename: R
authors.initials: R
authors.lastname: Zwerus
authors.forename: P H
authors.initials: PH
authors.lastname: Sykes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053607:Adrenomedullin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002392:Catechin / Q000031:analogs & derivatives / Q000378:metabolism; D045744:Cell Line, Tumor; D003035:Cobalt / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C507862:ADM protein, human; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013267:Stilbenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin; D003035:Cobalt; D002392:Catechin; C045651:epigallocatechin gallate; C018021:cobaltous chloride; D000077185:Resveratrol