| Summary: | The aim of this project was to investigate the potential involvement of endothelins in breast and ovarian cancer by (i) measuring the expression and secretion of endothelin by epithelial and fibroblast cell lines derived from ovarian and breast cancers, (ii) determining the expression of specific receptors for endothelins in the same cell lines, (iii) monitoring the effects of exogenous additions of endothelins on the growth of the cell lines in culture, (iv) measuring the expression of endothelins and their receptors in a series of primary ovarian and breast cancers. The growth of breast carcinoma cell lines was unaffected by the exogenous addition of ETs while ET-1 and ET-2 but not ET-3 addition stimulated the growth of ovarian carcinoma cells. Exogenous addition of ET-1, ET-2 and ET-3 stimulated the growth of both ovarian and breast fibroblast cell lines. The antagonists BQ123 (ET<SUB>A</SUB>-R antagonist) and BQ788 (ET<SUB>B</SUB>-R antagonist) inhibited ET-stimulated growth in a manner consistent with the receptor subtypes present in each cell line. In the absence of exogenous ET, the antagonists produced small inhibitory effects of growth in the ovarian carcinoma cell lines. This may be caused by the antagonism of ETs secreted by the same cells and could be consistent with autocrine stimulation of growth by endothelins. Co-culture of epithelial and fibroblast cells produced increased growth of both cell types relative to that when individual cell types were cultured separately. This indication, that increased growth could be blocked by addition of ET antagonists, suggests possible paracrine regulation of growth by ETs. These results support the view that endothelins may affect the growth of ovarian and breast tumours and these influences may operate through autocrine/paracrine loops.
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