Endothelin-1 as an autocrine/paracrine factor for human tumor cell lines

We determined whether endothelin-1 (ET-1) is produced and secreted by human tumor cell lines and whether ET-1 can affect cytosolic free Ca2+ concentrations ([Ca2+]i) in these cells. Dilution curves of extracts of cultured conditioned media from several human cancer cell lines (HeLa, HEp-2, DLD-1, and Ca9-22) were parallel to those of standard ET-1 in radioimmunoassay (RIA). Amounts of ET-1-like immunoreactivity released into conditioned media were reduced by omitting fetal bovine serum from culture media. Synthetic ET-1 dose-dependently induced gradual and sustained increases in [Ca2+]i in HeLa, HEp-2, GOTO, and Lovo cells, an effect completely abolished by a Ca2+ channel blocker or by chelating extracellular Ca2+. These data suggest an autocrine/paracrine role of ET-1 in human tumor cell lines.