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

Autor: Lynley K. Lewis, Peter Sykes, J.M. Dann, Parry Guilford, John J. Evans, J. Nagase, A.A.W. Welkamp, Kenny Chitcholtan, Gavin C. Harris, R. Zwerus
Přispěvatelé: Faculteit Medische Wetenschappen/UMCG
Rok vydání: 2011
Předmět:
Vascular Endothelial Growth Factor A
Angiogenesis
Estrogen receptor
HYPOXIA
Natural compound
ANGIOGENESIS
Catechin
chemistry.chemical_compound
Adrenomedullin
Endometrial cancer
Stilbenes
GENE-EXPRESSION
CARCINOMA CELLS
PLASMA
INDUCTION
Obstetrics and Gynecology
Cobalt
Up-Regulation
Vascular endothelial growth factor
Gene Expression Regulation
Neoplastic
Oncology
Female
hormones
hormone substitutes
and hormone antagonists
medicine.medical_specialty
POSSIBLE PROMOTION MECHANISM
Adenocarcinoma
Internal medicine
Cell Line
Tumor
medicine
Biomarkers
Tumor
Humans
Secretion
RNA
Messenger
Autocrine signalling
business.industry
Cancer
medicine.disease
Endometrial Neoplasms
AUTOCRINE
Endocrinology
ESTROGEN-RECEPTOR
chemistry
Resveratrol
Case-Control Studies
ENDOTHELIAL GROWTH-FACTOR
Neoplasm Grading
business
EGCG
Zdroj: Gynecologic Oncology, 125(1), 214-219. ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN: 1095-6859
0090-8258
Popis: 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.
Databáze: OpenAIRE
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