Production of Endothelin-1 and Big Endothelin-1 by Human Cardiac Myxoma Cells-Implications for the Origin of Myxomas-

Abstract

Although the origin of cardiac myxomas is still controversial, the 2 main hypotheses are that the tumor cells originate either from multipotential mesenchymal cells or from endocardial neural tissue. The production of various cytokines in 2 human cardiac myxoma cell lines was examined by enzyme-linked immunosorbent assay. After 7 days of culture, extremely high concentrations of interleukin-6 were detected in the culture media from both myxoma cell lines. Increased production of CXC chemokines, interleukin-8 and growth-related oncogene-alpha, were observed in both myxoma cell lines. Endothelin (ET)-1 and its precursor, big ET-1, were detected in the culture media from both myxoma cell lines. The production of both ET-1 and big ET-1 by myxoma cells was higher than by human umbilical vein endothelial cells. Similar to endothelial cells, myxoma cells did not produce stem cell factor, granulocyte colony-stimulating factor, hepatocyte growth factor, or ET-3. The similarity of the cytokine production pattern between cardiac myxoma cells and endothelial cells supports the hypothesis that the tumor cells originate from mesenchymal cells capable of endothelial differentiation. Overproduction of CXC chemokines may explain, in part, the malignant potential of histologically benign myxomas.