Exp Clin Endocrinol Diabetes 2006; 114 - P14_174
DOI: 10.1055/s-2006-933059

Effects of endothelial cell products on the proliferation of human adrenocortical cancer cells

I Paramonova 1, S Schinner 1, C Papewalis 1, M Schott 1, SR Bornstein 2, WA Scherbaum 1, HS Willenberg 1
  • 1University Hospital Düsseldorf, Dept. of Endocrinology, Diabetes and Rheumatology, Düsseldorf, Germany
  • 2Carl Gustav Carus University, University Clinic III, Dresden, Germany

Objectives: The circulatory system of the adrenal gland provides a lot of contacts between endothelial and adrenocortical cells. Both cell types produce various factors and are thought to interact with each other. Endothelin (ET)-1 has been shown to interfere with adrenal cell growth via the ET-A receptor. The purpose of this study was to investigate regulatory actions of endothelial cell products other than ET-1 on parameters of tissue growth in adrenocortical cells.

Methods: Adrenocortical carcinoma NCI-H295R cells have been incubated with endothelial cell-conditioned medium (ECCM) that was produced by HUVEC cells. In addition, the effect on the proliferation of NCI-H295R cells was measured at different concentrations of ECCM (0%, 1%, 5%,10%, 20%, 50%, and 100%), as assayed by WST-1, tritium-thymidine-incorporation. Furthermore, we assessed the regulation of the promoter of the cyclin D gene, a known cell cycle regulator, by ECCM.

Results: Incubation of NCI-H295R cells with ECCM led to an increased rate of proliferation (150%-200%) in a concentration- and time-dependent manner. Maximal values were achieved with ECCM-concentrations of 20–30%. The effect on proliferation of the adrenocortical cells could not be inhibited by BQ123 and BQ-788, antagonists of the ET-A and ET-B receptor subtypes, respectively, when added at concentrations of 10(-9)M.

Conclusion: Our results show that endothelial cell products stimulate the proliferation of adrenocortical cells in vitro and that cyclin D may be involved in mediating the proliferative effects. Therefore, endothelial cell-derived factors may play a role in adrenal embryogenesis and in the pathogenesis of adrenal tumor growth. In addition, our data suggest that the proliferative effects on the adrenocortical cells are mediated by factors other than endothelin-1.