Production of Endothelin-1 and Big-Endothelin-1 by Tumor Cells with Epithelial-Like Morphology

Publisher Website
Google Scholar
Abstract
Immunoreactive endothelin (ET) and big-endothelin (big-ET) in conditioned media of endothelial and of non-endothelial cells were studied using sandwich-type enzyme im-munoassays. Immunoreactivities of both ETs were detected in the media of all four endothelial cells tested. Among non-endothelial cells, tumor cell lines with epithelial-like morphology also produced immunoreactive ET and/or big-ET, although the total amount of ETs was one or two orders of magnitude less than that produced by PAE (porcine aortic endothelial cells). Immunoreactive ETs produced by HepG-2 (human hepatocellular carcinoma) and some other cells were characterized by gel-filtration HPLC and reverse-phase HPLC. These studies revealed the production of ET-1 and human big-ET-1 by these cells, although the immunoreactive ETs produced by the tumor cells were more heterogeneous than those produced by endothelial cells. The regulatory effects of thrombin and transforming growth factor-β (TGF-β) on the production of ETs were investigated. TGF-β markedly stimulated the production of both ETs in HepG-2 and slightly decreased the big-ET level in A549 (human lung carcinoma). HPLC analysis showed that the major immunoreactive ETs induced by TGF-β in HepG-2 were identical to ET-1 and human big-ET-1. These results demonstrated that production of ET-1 and big-ET-1 was not restricted to endothelial cells and was induced by TGF-β in HepG-2 at the same levels as those produced by PAE.

This publication has 12 references indexed in Scilit: